Studien

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Ferras Alashkar

+49 (0)201 723-82530
ferras.alashkar@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Agios Pharmaceuticals Inc., USA

Einschlusskriterien
• Age ≥16 years; subjects age 16 or 17 years must physically have completed puberty.
• Documented diagnosis of SCD (HbSS, HbSC, HbS/β0-thalassemia, HbS/β+ thalassemia, or other sickle cell syndrome variants).
• At least 2 sickle cell pain crises (SCPCs) and no more than 10 SCPCs in the past 12 months.
• Hemoglobin ≥5.5 and ≤10.5 g/dL.
• If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug.
• Women capable of becoming pregnant and men with partners who are women that are capable of becoming pregnant must agree to use 2 forms of contraception.
• Other protocol-defined inclusion criteria may apply.

Ausschlusskriterien
• Pregnant or breastfeeding.
• Receiving regularly scheduled transfusions.
• Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease.
• Severe kidney disease.
• Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.
• Currently receiving treatment for SCD (eg, voxelotor, crizanlizumab, L glutamine), with the exception of hydroxyurea. The last dose of such therapies must have been administered at least 90 days before starting study drug.
• Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug.
• Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial.
• Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor).
• Other protocol defined exclusion criteria may apply.

Studienteilnehmende Mindestalter
16 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Anämie

Medizinischer Befund
Sickle Cell Disease

MedDRA Term
Sickle Cell Disease

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Klinikum der Universität München, Klinikum Großhadern

Einschlusskriterien
AML gemäß den WHO-Diagnose-Kriterien, einschließlich Akute Promyelozyten-leukämie (APL)
Alter ≥18 Jahre
unterschriebene Einwilligungserklärung

Ausschlusskriterien
keine

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
AML - Akute myeloische Leukämie

Medizinischer Befund
AML

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Richard Noppeney

+49 (0)201 723-82530
richard.noppeney@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universität Leipzig

Einschlusskriterien
- newly-diagnosed APL (either de novo or therapy-related), within 12 months of diagnosis or relapsed APL, within 12 months of diagnosis of relapse
- confirmed by the presence of the translocation t(15; 17) and/or confirmed by the detection of the fusion transcript of PML/RARa

Ausschlusskriterien
none

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
APL - Promyelozytenleukämie

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum, WTZMS - Westdeutsches Tumorzentrum Münster

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Richard Noppeney

+49 (0)201 723-82530
richard.noppeney@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Technische Universität Dresden

Einschlusskriterien
- Informed consent
- women or man with a newly diagnosed APL by cytomorphology, confirmed by molecular analysis
- Age ≥18 and ≤ 65 years
- ECOG performance status 0-3
- WBC at diagnosis > 10 GPt/l
- serum total bilirubin ≤ 3.0 mg/dl (≤ 51 µmol/l)
- serum creatinine ≤ 3.0 mg/dl (≤ 260 µmol/l)
- women must fulfill at least one of the following criteria in order to be eligible for trial inclusion:
o Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml)
o Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy
o Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device – IUD).
o Sexual abstinence
o Vasectomy of the sexual partner

Ausschlusskriterien
- patients who are not eligible for chemotherapy as per discretion of the treating physician
- APL secondary to previous radio- or chemotherapy for non-APL disease
- other active malignancy at time of study entry (exception: Basal-Cell Carcinoma)
- lack of diagnostic confirmation of APL at genetic level
- Significant arrhythmias, ECG abnormalities
- other cardiac contraindications for intensive chemotherapy (L-VEF <50%)
- uncontrolled, life-threatening infections
- severe non controlled pulmonary or cardiac disease
- severe hepatic or renal dysfunction
- HIV and/or active hepatitis C infection
- pregnant or breast-feeding patients
- allergy to trial medication or excipients in study medication
- substance abuse; medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results
- use of other investigational drugs at the time of enrolment or within 30 days before study entry

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
65 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
APL - Promyelozytenleukämie

Medizinischer Befund
newly diagnosed high-risk acute promyelocytic leukemia (APL)

MedDRA Term
Acute promyelocytic leukaemia

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universität des Saarlandes

Studienteilnehmende Mindestalter
60 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
DLBCL - Diffuses großzelliges B-Zell-Lymphom

Medizinischer Befund
Diffuse Large B-cell lymphoma (DLBCL)

Institute
Klinik für Neurologie, Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Refik Pul

refik.pul@uk-essen.de

Hufelandstr 55
45147 Essen

Sponsor

Bristol-Myers Squibb GmbH & Co. KGaA

Arnulfstraße 29
80636 München

Einschlusskriterien
- Relapsing forms of Multiple Sclerosis (RMS) - Cohort 1.
i) Participants must have an Expanded Disability Status Scale (EDSS) of ≥ 3.0 and ≤ 5.5.
ii) Participants must have a diagnosis of Multiple Sclerosis (MS) with relapsed/refractory MS or conversion to active secondary progressive multiple sclerosis (aSPMS), and worsening of disease within 12 months prior to Screening and while on treatment with a high-efficacy DMT for at least 6 months.
- Progressive forms of MS - Cohort 2.
i) Participants must have an EDSS ≥ 3.0 and ≤ 6.0.
ii) Participants must have a diagnosis of primary progressive multiple sclerosis (PPMS) that is treatment-resistant or diagnosis of inactive secondary progressive multiple sclerosis (iSPMS).

Ausschlusskriterien
- Participants that cannot complete the 9-Hole Peg Test (9-HPT) for each hand in <240 seconds.
- Participants that cannot perform a Timed 25-Foot Walk Test (T25FWT) in < 150 seconds.
- Participants must not have MS lesions or symptoms that may place patients at increased risk of neurotoxicity, including, but not limited to, tumefactive lesion (3 cm or greater within 5 years prior to Screening) or decreased level of consciousness, and/or presence of active, clinically significant concomitant central nervous system pathology other than MS that may confound the ability to interpret study results or complicate identification or evaluation of neurotoxicity.
- Other protocol-defined Inclusion/Exclusion criteria apply.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
60 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
MS - Multiple Sklerose, Phase I Studie

Medizinischer Befund
Relapsing Multiple Sclerosis (RMS)\nMyasthenia gravis (MG)\nProgressive Multiple Sclerosis (PMS)

MedDRA Term
Multiple sclerosis, Myasthenia gravis, Relapsing multiple sclerosis, Progressive multiple sclerosis

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

+49 (0)201 723-82530
alexander.roeth@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
1. Patient aged =18 years
2. Patient able to understand the purpose of the study and who (or whose legally authorized representative) provided signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations
3. Patient with a diagnosis of CAD or CAS as per Investigator judgment based on the diagnosis criteria listed in study protocol

Ausschlusskriterien
1. Patient with mixed warm and cold autoimmune hemolytic anemia, or warm autoimmune hemolytic anemia
2. Patient actively participating in a CAD or CAS interventional clinical trial. After a patient completes participation in said trial, he/she may be eligible for enrollment in this registry.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
CAD – Kälteagglutinin-Krankheit

Medizinischer Befund
Cold Agglutinin Disease (CAD)\nCold Agglutinin Syndrome (CAS)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Klinikum LMU München

Indikation
MCL - Mantelzelllymphom

Institute
Klinik für Hämatologie und Stammzelltransplantation, Klinik für Kinderheilkunde III, Westdeutsches Tumorzentrum, WTZMS - Westdeutsches Tumorzentrum Münster

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Nina Kristin Steckel

+49 (0)201 723-3712
nina-kristin.steckel@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Novartis Pharma Schweiz AG

+41 41 763 71 11

Suurstoffi 14
6343 Rotkreuz

Einschlusskriterien
- Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or
cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible
- Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive
therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
- Confirmed diagnosis of corticosteroid refractory aGvHD (confirmed within 48h prior to study treatment start) defined as:
• Patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
• Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,
OR
• Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,
OR
• Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:
• Requirement for an increase in the corticosteroid dose to methylprednisolone =2 mg/kg/day (or equivalent prednisone dose =2.5 mg/kg/day)
OR
• Failure to taper the methylprednisolone dose to <1 mg/kg/day (or equivalent prednisone dose <1.25 mg/kg/day) for a minimum 7 days.

Ausschlusskriterien
- Has received more than one systemic treatment for steriod refractory aGvHD,
- Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features (as defined by Jagasia, et al. 2015)
- Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection.
Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Evidence of uncontrolled viral infection including CMV, EBV, HHV-6, HBV, or HCV based on assessment by the treating physicial.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
Other protocol-defined inclusion/exclusion criteria may apply.

Geschlecht
Männlich, Weiblich

Indikation
KIK-Onko

Medizinischer Befund
corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantation

MedDRA Term
Acute graft versus host disease in skin, Acute graft versus host disease, Acute graft versus host disease in intestine, Acute graft versus host disease in liver

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Stephanie Sasse

+49 (0)201 723-82530
stephanie.sasse@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Universitätsklinikum Köln

Einschlusskriterien
1. Confirmed diagnosis of CLL according to iwCLL criteria (Hallek et al, 2018)
2. Confirmed histopathological diagnosis of RT (diffuse large B-cell lymphoma or Hodgkin's lymphoma [Hodgkin's lymphoma only when not eligible for more in-tensive treatment])
3. Previously untreated RT or patients with objective response or non-tolerance to first-line RT treatment
4. Adequate bone marrow function as defined by:
o Absolute neutrophil count (ANC) = 1000/mm3, except for patients with bone marrow involvement in which ANC must be = 500/mm3
o Platelet = 75,000/mm3, except for patients with bone marrow involvement in which the platelet count must be = 30,000/mm3
5. Creatinine clearance =30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection or an equivalent method.
6. Adequate liver function as indicated by a total bilirubin= 2 x, AST/ALT = 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL/RT or to Gilbert's Syndrome, in which case a max. total bilirubin = 3 x and AST/ALT = 5 x the institutional ULN value are required.
7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc nega-tive; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every two months until 2 months af-ter last dose of zanubrutinib), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
8. Age at least 18 years
9. ECOG performance status 0-2, ECOG 3 is only permitted if related to CLL or RT (e.g. due to anaemia or severe constitutional symptoms)
10. Life expectancy = 3 months
11. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Ausschlusskriterien
1. Patients who did not respond to previous line of RT therapy (i.e. primary progressive patients)
2. Patients with more than one prior line of RT therapy
3. Allogenic stem cell transplantation within the last 100 days or signs of active GVHD after prior allogeneic stem cell transplantation within any time
4. Patients with confirmed PML
5. Uncontrolled autoimmune condition
6. Malignancies other than CLL currently requiring systemic therapies (unless the malignant disease is in a stable remission at the discretion of the treating phy-sician)
7. Uncontrolled infection currently requiring systemic treatment
8. Any comorbidity or organ system impairment rated with a CIRS (cumulative ill-ness rating scale) score of 4, excluding the eyes/ears/nose/throat/larynx organ system , or any other life-threatening illness, medical condition or organ system dysfunction that - in the investigator´s opinion could comprise the patients safety or interfere with the absorption or metabolism of the study drugs
9. Requirement of therapy with strong CYP3A4 inhibitors/ inducers
10. Requirement of therapy with phenprocoumon or other vitamin K antagonists.
11. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
o Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core anti-body (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation.
o Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
12. Major surgery within 4 weeks of the first dose of study drug.
13. Any uncontrolled or clinically significant cardiovascular disease including the following:
o Myocardial infarction within 6 months before screening
o Unstable angina within 3 months before screening
o New York Heart Association class III or IV congestive heart failure
o History of clinically significant arrhythmias (eg, sustained ventricular tachy-cardia, ventricular fibrillation, torsades de pointes)
14. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood trans-fusion or other medical intervention
15. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
16. Severe or debilitating pulmonary disease
17. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
18. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration
19. Known hypersensitivity to tislelizumab, zanubrutinib, sonrotoclax or any of the excipients
20. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment)
21. Fertile men or women of childbearing potential unless:
o surgically sterile or = 2 years after the onset of menopause, or
o willing to use two methods of reliable contraception including one highly ef-fective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 6 months after the end of study treatment.
22. Vaccination with a live vaccine <28 days prior to randomization
23. Legal incapacity
24. Prisoners or subjects who are institutionalized by regulatory or court order
25. Persons who are in dependence to the sponsor or an investigator

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
CLL - Chronische lymphatische Leukämie

Medizinischer Befund
Richter Transformation\nPatients with previously untreated Richter Transformation or patients who responded to up to one prior line of RT therapy

MedDRA Term
Chronic lymphocytic leukaemia variants

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Stephanie Sasse

+49 (0)201 723-82530
stephanie.sasse@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Deutsche CLL Studiengruppe (DCLLSG), Universitätsklinik Köln

Einschlusskriterien
01. Documented CLL/SLL³ requiring treatment according to iwCLL criteria1.
02. Age at least 18 years.
03. At least one of the following risk factors: 17p- deletion, TP53 mutation, complex karyotype (defined as defined as the presence of 3 or more chromosomal aberrations in 2 or more metaphases.
04. Life expectancy ≥ 6 months.
05. Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2.
06. Ability and willingness to provide written informed consent and to adhere to the study visitschedule and other protocol requirements.
07. Adequate bone marrow function indicated by a platelet count >30 x10^9/l (unless directlyattributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy).
08. GFR >30 ml/min directly measured with 24hr urine collection, calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight) / (72 x creatinine), for women x 0, 85) or an equally accurate method. For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 30 ml/min may be eligible if a repeat estimate after adequate hydration is > 30 ml/min.
9. Adequate liver function as indicated by a total bilirubin ≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome.
10. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBVDNA PCR is performed every month until 12 months after last treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration.

³ Patients with SLL are eligible with confirmation of clonal b-cells in the peripheral blood by immunophenotyping. Patients with
SLL without any leukemic manifestation are not eligible.

Ausschlusskriterien
01. Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents up to 20 mg prednisolone are permitted).
02. Transformation of CLL (Richter‘s transformation).
03. Known central nervous system involvement.
04. An individual organ/system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system (note that symptoms related to CLL should not be included in the patient’s screening CIRS score). Investigators should consult the General Rules for Severity Rating as well as the Organ-Specific Categories when assigning scores for certain conditions (i.e., pulmonary embolism) and consider the level of morbidity associated with a patient’s condition. Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator’s opinion, could compromise the subject’s safety or put the study at risk.
05. Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of prednisolone or intravenous immunoglobulins (IVIG) being administered for hemolysis. Prior treatment with rituximab also for other indications than CLL is not permitted.
06. Patients with a history of confirmed progressive multifocal leukoencephalopathy.
07. Malignancies other than CLL currently requiring systemic therapies, not being treated with curative intent before (unless the malignant disease is in a stable remission due to the discretion of the treating physician) or showing signs of progression after curative treatment.
08. Patients with active infections requiring IV treatment (Grade 3 or 4) within the last 2 months prior to enrollment.
09. Patients with known infection with human immunodeficiency virus (HIV).
10. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers.
11. Anticoagulant therapy with warfarin or phenoprocoumon, (alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly informed
about the potential risk of bleeding under treatment with acalabrutinib).
12. Requirement of treatment with a PPI (proton pump inhibitor). If treatment with an acid reducing agent is required, consider using an antacid (e.g., calcium carbonate) or an H2- receptor antagonist (e.g. ranitidine or famotidine) instead.
13. History of stroke or intracranial hemorrhage within 6 months prior to registration.
14. Use of investigational agents which might interfere with the study drug within 28 days prior to registration.
15. Vaccination with live vaccines 28 days prior to registration.
16. Major surgery less than 30 days before start of treatment.
17. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
18. Known hypersensitivity to any active substance or to any of the excipients of one of the
drugs used in the trial.
19. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly see chapter 2.3.1.5).
20. Fertile men or women of childbearing potential unless:
a. surgically sterile or = 2 years after the onset of menopause.
b. willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment.
21. Inability to swallow a large number of tablets.
22. Legal incapacity.
23. Prisoners or subjects who are institutionalized by regulatory or court order or persons who are in dependence to the sponsor or an investigator.

Studienteilnehmende Mindestalter
18 Jahr(e)

Indikation
CLL - Chronische lymphatische Leukämie

Medizinischer Befund
Chronic lymphocytic leukemia (CLL): High risk patients defined as having at least one of the following risk factors: 17p-deletion, TP53-mutation or complex karyotype

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

+49 (0)201 723-82530
alexander.roeth@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Novartis Pharma Schweiz AG

+41 41 763 71 11

Suurstoffi 14
6343 Rotkreuz

Einschlusskriterien
Participants eligible for inclusion in this study must meet all of the following criteria:
1a. Signed informed consent prior to participation in the study.
2a. Male or female participants aged 18 years and older on the day of signing informed consent
3a. Primary ITP diagnosed within 3 months before initiating first-line ITP therapy (corticosteroids, IVIG).
4. Platelet count below 30 G/L before starting any first-line ITP therapy (corticosteroids, IVIG).
5. Response (platelet count ≥50 G/L) to corticosteroids (+/- IVIG) at any time prior to randomization. Note: Platelet counts measured within 7 days of platelet transfusion will not be considered as response.

Ausschlusskriterien
Participants meeting any of the following criteria are not eligible for inclusion in this study.
1. Evans syndrome or any other cytopenia
2. Current life-threatening bleeding
3a. Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG for up to 28 days before randomization
4a. Prior use of B-cell depleting therapy (e.g., rituximab).
6a. Absolute neutrophil count below 1.0 G/L at randomization.
7a. Participants with concurrent coagulation disorders and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (see Prohibited medications in Section 6.8.2)
9. 8a. Active viral, bacterial or other infections (including tuberculosis -TB) requiring systemic treatment or SARS-CoV-2 infection during the screening period, or history of recurrent clinically significant infection (eg. bacterial infections with encapsulated organisms). Participants with positive hepatitis C virus antibody (HCV Ab) antibody, hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb)
10. Known history of primary or secondary immunodeficiency, or a positive HIV (ELISA and Western blot) test result
11. Live or live-attenuated vaccination within 4 weeks before randomization
12. Nursing or pregnancy (positive serum or urine B-human chorionic gonadotrophin (ß-hCG) pregnancy test) at screening or pre-dose on Day 1
13. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after last dose of ianalumab. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• For female participants on the study, the vasectomized male partner should be the sole partner for that participant
• Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women are considered not of child-bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks prior to enrollment on study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child-bearing potential. If local regulations are more stringent from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the informed consent form (ICF).
14. Previous or concurrent malignancy except for curatively treated non-melanoma skin cancer, in situ cancer (e.g., cervix, breast, bladder, prostate), and cancer in complete remission for at least 3 years and without evidence of recurrence
15. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with participants' safety and efficacy, obtaining informed consent or compliance with the study procedures as per investigator discretion
16. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to ianalumab or drugs chemically related to ianalumab or excipients that contraindicate their participation
17a. Concurrent participation in an investigational study within 30 days prior to randomization or within 5-half-lives of the investigational product, whichever is longest. Note: parallel enrollment in a disease registry is permitted.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
ITP - idiopathische thrombozytopenische Purpura

Medizinischer Befund
Primary Immune thrombocytopenia (ITP)

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

+49 (0)201 723-82530
alexander.roeth@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Novartis Pharma Schweiz AG

+41 41 763 71 11

Suurstoffi 14
6343 Rotkreuz

Einschlusskriterien
Participants eligble for inclusion in this study must meet all of the following criteria:
1. Written informed consent must be obtained prior to any screening procedures.
2. Male or female patients aged 18 years and older on the day of signing informed consent.
3. Participants with primary or secondary wAIHA, as previously documented by a positive direct antiglobulin test (DAT) specific for anti-IgG or anti-IgA, who had an insufficient response to, or relapsed after at least one line of treatment, including patients with steroid resistance, dependence or intolerance.
Steroid resistance: failure to obtain hematologic response within 3 weeks on at least 1 mg/kg predniso(lo)ne (up to 60 mg daily in participants weighing over 60 kg).
Steroid dependence: Need to continue predniso(lo)ne at a dose of >10 mg/day to maintain a reponse.
Steroid intolerance : side effects or anaphylactic/ anaphylactoid reactions which lead to permanent termination of steroids.
4. Hemoglobin concentration at screening below 10 g/dl, associated with presence of symstoms related to anemia.
5. The dose of supportive care (see Section 6.8.1.1) must be stable for at least 4 weeks prior to the randomization into the study.

Ausschlusskriterien
Participants meeting any of the following criteria are not eligible for inclusion in this study.
1. Patients with wAIHA secondary to hematologic disease involving bone marrow (e.g., CLL) or other immunologic disease requiring immunosuppressant treatments that are not allowed in this study (please refer to Section 6.8.2 Prohibited Medication).
2. Presence of other forms of AIHA (cold or intermediate forms), Evans Syndrome or other cytopenias.
3. Prior use of B-cell depleting therapy (e.g., rituximab) withing 12 weeks prior to randomization.
If other immunosuppressive therapies were used prior the screening, a wash-out period should be applied (see SEction 10.8 for details)
4. (removed)
5. Patients with following conditions at screening:
- Neutrophils <1000/mm³
- Serum creatinine >1.5 x upper limit of normal (ULN)
6. Active viral, bacterial or other infections (including tuberculosis -TB or SARS-CoV-2) requiring systemic treatment at the time of screening or history of recurrent clinically significant infection (e.g., bacterial infections with encapsulated organisms).
7. Positivity for hepatis C virsu (concomitans positivity for HCV antibodies), hepatitis B surface antigen (HbsAG), or hepatitis B core antibody (HbcAB) at screening.
8. Known history of primary or secondary immunodeficientcy, or a positive human immune deficiency virus (HIV) (ELISA and Western blot) test result at screening.
9. Live or live-attenuated vaccination within 4 weeks before randomization.
10. Nursing or pregnancy (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1.
11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods off controception during the study and until six month after last dose of study drug. Highly effective contraception methods include:
Total abstinence (when this is in line with the preferred an usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptohermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy, with or without hysterectomy), total hysterectomy or female bilateral tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
Use of oral, (estorgen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 month before taking investigational drug. Women are considered postmenopausal if they have had 12 month of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasamotor symptoms). Women are considered not of child-bearing potential, if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks prior to enrllment in study. In the case of oophorectomy alone, only when the reproductive status of the women has been confirmed by follow-up hormone level assessment is she considered not of child-bearing potential. If local regulations are monre stringend from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the informed consent form (ICF).
12. Previous or concurrent malignancy expect for curatively treated non-melanoma skin cancer, in situ cancer (e.g., cervix, breat, bladder, prostate), and cancer in complete remission for at least 3 years and without evidence of recurrence.
13. History of splenectomy.
14. Any serious an/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with patient's efficacy, safety, obtaining informed consent or compliance withe study procedures as per investigator discretion.
15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to ianalubmab or drugs chemically related to ianalumab or excipients that contraindicate ther participation.
16. Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longest. Note: parallel enrollment in a disease registry is permitted.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Waiha – Autoimmunhämolytische Anämie vom Wärmetyp

Medizinischer Befund
warm autoimmune haemolytic anaemia (wAIHA)

MedDRA Term
Warm type haemolytic anaemia

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Novartis Pharmaceuticals

+1 888-669-6682
novartis.email@novartis.com

1000 S Pine Island Rd #410
33324 Florida

Einschlusskriterien
- ECOG performance status 0-1
- CLL or SLL diagnosis according to iwCLL criteria
- CLL/SLL in SD or PR after at least 6 months of ibrutinib, either as second or subsequent line of therapy
- DLBCL diagnosis by local histopathology
- DLBCL relapsed or refractory after 2 or more lines of therapy, including autologous hematopoietic stem cell transplantation (HSCT)
- Refractory or relapsed CD19-positive ALL
- ALL with morphologic disease in the bone marrow 1L HR LBCL - Considered to be high-risk based on at least 1 of the following at diagnosis:
-- IPI score of 3, 4 or 5
-- MYC and BCL2 and/or BCL6 rearrangement (DH/THL)
- Participants must have received 2 cycles of frontline therapy for LBCL with R-CHOP or Pola-R-CHP or DA-EPOCH-R. Participants with DH/TH lymphoma must have received DA-EPOCH-R.
- Participants must have a positive PET per Lugano classific

Ausschlusskriterien
- Prior CD19-directed therapy
- Prior administration of a genetically engineered cellular product
- Prior allogeneic HSCT
- Richter's transformation
-- For 1L HR LBCL: Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, DLBCL associated with chronic inflammation, intravascular large B-cell lymphoma, ALK- positive large B-cell lymphoma, HHV8 positive LBCL, DLBCL leg type or EBV positive DLBCL, NOS.
- Active CNS lymphoma
-- For 1L HR LBCL: Active CNS involvement by malignancy
- Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ALL - Akute lymphatische Leukämie, CLL - Chronische lymphatische Leukämie, DLBCL - Diffuses großzelliges B-Zell-Lymphom, SLL - kleinzelliges lymphozytisches Lymphom

Medizinischer Befund
Chronic Lymphocytic Leukemia\nSmall Lymphocytic Lymphoma\nDiffuse Large B-cell Lymphoma\nAcute Lymphoblastic Leukemia\nLarge B-cell Lymphoma

MedDRA Term
Acute lymphocytic leukaemia, Primary mediastinal large B-cell lymphoma, High-grade B-cell lymphoma, Chronic lymphocytic leukaemia, Follicular lymphoma, Diffuse large B-cell lymphoma, B-cell small lymphocytic lymphoma

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Deutsche Krebshilfe e.V.

+49 (0)228 72990-0
deutsche@krebshilfe.de

Buschstr. 32
53113 Bonn

Einschlusskriterien
• Histologisch gesicherte Erstdiagnose eines Hodgkin-Lymphoms
• Patientin/Patient ist in Bezug auf das HL therapienaiv
• Schriftliche Einverständniserklärung zur Teilnahme an der Studie vorliegend
• Patientin/Patient ist damit einverstanden, dass die personenbezogenen Daten unter Wahrung des Datenschutzes der Studie zur Verfügung gestellt werden.

Ausschlusskriterien
• Unfähigkeit, sich auf Deutsch zu verständigen
• mangelnde Compliance

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
60 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
HD - Hodgkin Lymphom

Medizinischer Befund
Hodgkin-Lymphom Lymphogranulomatose

Institute
Klinik und Poliklinik für Strahlentherapie, Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Stephanie Sasse

+49 (0)201 723-82530
stephanie.sasse@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Ruprecht-Karls-Universität Heidelberg

Einschlusskriterien
• Centrally reviewed CD20-positive follicular lymphoma grade 1/2 or 3a based on WHO classification (2008)
• Untreated (radiation-, chemo- or immunotherapy) nodal follicular lymphoma (including involvement of Waldeyer´s ring)
• Age: ≥18 years
• ECOG: 0-2
• Stage: clinical stage I or II (Ann Arbor classification) based on FDG-PET Staging
• Risk profile: Largest diameter of the lymphoma ≤ 7 cm (sectional images)
• Written informed consent and willingness to cooperate during the course of the trial
• Adequate bone marrow capacity: ANC ≥ 1.5 x 103/ml, thrombocytes ≥ 100000 x 10 3/ml, hemoglobin ≥ 10 g/dL
• Capability to understand the intention and the consequences of the clinical trial
• Adequate contraception for men and women of child-bearing age during therapy and 18 months thereafter

Ausschlusskriterien
• Extra nodal manifestation of follicular lymphoma
• Secondary cancer in the patient's medical history (exclusion: basalioma, spinalioma, melanoma in situ, bladder cancer T1a, non-metastasized solid tumor in constant remission, which was diagnosed >3 years ago)
• Serious disease interfering with a regular therapy according to the study protocol, e.g: congenital or acquired immune-deficiency syndromes, active infections including viral hepatitis, uncontrolled concomitant diseases including significant cardiovascular or pulmonary disease
• Severe psychiatric disease
• Pregnancy / lactation
• Known hypersensitivity against Obinutuzumab or Rituximab drugs with similar chemical structure or any other additive of the pharmaceutical formula of the study drug
• Active hepatitis B infection (inactive hepatitis B infections require additional prophylactic anti-viral medication for 1 year (e.g. Lamivudin, Entecavir, Tenofovir)
• Participation in another interventional trial or follow-up period of a competing trial which can influence the results of this current trial
• Creatinine > 1.5 times the upper limit of normal (ULN)
(unless creatinine clearance normal), or calculated
creatinine clearance < 40 mL/min
• AST or ALT > 2.5 × ULN
• Total bilirubin = 1.5 × ULN
• INR > 1.5 × ULN
• PTT or aPTT > 1.5 × the ULN

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
nodal follicular lymphoma grade 1 or grade 2 in the clinical stage I or II (Ann Arbor classification)

MedDRA Term
Non-Hodgkin's lymphoma stage II, Non-Hodgkin's lymphoma stage I

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Goethe-Universität, Frankfurt

Einschlusskriterien
Patients must meet inclusion criteria to be eligible to enroll in this study:
1. Age ≥ 18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
3. Availability of patient-specific molecular MRD markers of immunoglobulin/T-cell receptor gene rearrangements as assessed with a sensitivity of at least 10E-04
4. Diagnosis of Ph-negative, CD19-positive B-precursor acute lymphoblastic leukemia
according to WHO classification:
 Refractory BCP-ALL to primary induction therapy, including at least three cycles of standard chemotherapy
 Untreated first relapse of BCP-ALL with first remission duration < 12 months or
 Second or greater relapse of BCP-ALL or refractory relapse or
 Relapse of BCP-ALL any time after allogeneic HSCT or
 Positivity of MRD marker of immunoglobulin/T-cell receptor gene rearrangements of greater than 0.1% if in first or second remission of BCP-ALL
5. Willingness to participate in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Ausschlusskriterien
Selected Exclusion Criteria:
Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
1. Patients with diagnosis of Philadelphia positive BCP-ALL according to WHO classification
2. Patients with diagnosis of Burkitt´s Leukemia according to WHO classification
3. Patients with extramedullary relapse; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted
4. Patients with CNS involvement at relapse (as determined by CSF analysis)
5. Patients with suspected or histologically confirmed testicular involvement at relapse
6. Current autoimmune disease of any kind or history of autoimmune disease with potential CNS involvement
7. Prior or concomitant therapy with BH3 mimetics
8. Prior therapy with anti CD19 therapy, unless administered in MRD-positive setting (i.e. with bone marrow blasts = 5%)
9. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis. History of CNS leukemia that is controlled at relapse may be enrolled in this study.
10. History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of:
11. Malignancy treated with curative intent and with no known active disease present for 2 years before enrollment and felt to be at low risk for recurrence by the treating physician including
12. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
13. Adequately treated cervical carcinoma in situ without evidence of disease
14. Adequately treated breast ductal carcinoma in situ without evidence of disease
15. Prostatic intraepithelial neoplasia without evidence of prostate cancer.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
ALL - Akute lymphatische Leukämie

Medizinischer Befund
relapsed\/refractory B cell precursor acute lymphoblastic leukemia (BCP-ALL)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Goethe-Universität, Frankfurt

Einschlusskriterien
• Male or female patients >= 18 years, <=65 years
• Philadelphia chromosome or BCR-ABL1 positive ALL
• Not previously treated except with corticosteroids = 7 days, standard GMALL prephase with dexamethasone and cyclophosphamide including intrathecal therapy, hydroxyurea, a single dose vincristine or other cytostatic drugs and start of standard induction for Ph-positive ALL (1 dose vincristine, 1 dose of Rituximab, 2 doses dexamethasone and up to 5 days Imatinib)
• ECOG performance status =2
• Signed written inform consent
• Molecular evaluation for BCR-ABL1 performed
• Negative pregnancy test in women of childbearing potential
• Woman of childbearing potential willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment (Pearl-Index <1%). Male who has a female partner of childbearing potential willing to use 2 highly effective forms of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment (Pearl-Index <1%).
• Normal serum levels > LLN (lower limit of normal) of potassium and magnesium, or corrected to within normal limits with supplements, prior to the first dose of study medication
• Serum lipase = 1.5 x ULN. For serum lipase > ULN - = 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis
• Normal QTcF interval =450 ms for males and =470 ms for females
• Signed and dated written informed consent is available
• Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Ausschlusskriterien
• History of malignancy other than ALL diagnosed within 5 years (yrs) prior to start of protocol-specified therapy with defined exceptions
• Contraindications against the use of Imatinib, Ponatinib, chemotherapy or Blinatumomab
• Patient previously treated with tyrosine kinase inhibitors
• Nursing women
• Known impaired cardiac function, including any of the following: as detailed in protocol
• Symptomatic peripheral vascular disease
• Any history of ischemic stroke or transient ischemic attacks (TIAs)
• Uncontrolled hypertriglyceridaemia
• History or presence of clinically relevant CNS pathology as detailed in protocol
• History or active relevant autoimmune disease
• Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C
• History of pancreatitis within 6 months previous to start of treatment within the trial
• Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
• Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
• Total bilirubin > 1.5-fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
• Concurrent severe diseases which exclude the administration of therapy e.g. severe, uncontrolled acute or chronic infections
• Inability to understand and/or unwillingness to sign a written informed consent

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
65 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ALL - Akute lymphatische Leukämie

Medizinischer Befund
Blut: Akute lymphatische Leukämie (ALL): Neu diagnostiziert \/ de novo\n\nPhiladelphia Chromosome Positive Acute Lymphoblastic Leukemia

MedDRA Term
Acute lymphatic leukemia, Acute lymphatic leukaemia

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

GMALL-Studiengruppe

hoelzer@em.uni-frankfurt.de

Schaubstr. 16
60596 Frankfurt

Einschlusskriterien
# Alter mind. 18 Jahre
# Schriftliche Einverständniserklärung des Patienten
# Therapie analog zu einer GMALL Therapieoptimierungsstudie oder einer GMALL-Therapieempfehlung
# Eine der folgenden drei Einschlusskriterien:
# 1. akute lymphatische Leukämie
# 2. andere Leukämien (NK-Zell-Lymphom/Leukämie oder akute biphänotypische Leukämie)
# 3. Non-Hodgkin-Lymphome folgender Subtypen (WHO-Klassifikation): Burkitt-Lymphom (inkl. atypisches Burkitt-Lymphom, Burkitt-like-Lymphom), diffus großzellige B-Zell-Lymphome (insbesondere primär mediastinale DLBCL, DLBCL mit Burkitt-Signatur, c-myc-positive DLBCL), B-lymphoblastisches Lymphom, T-lymphoblastisches Lymphom, Großzellig-anaplastisches Lymphom, Sonstige NHL

Ausschlusskriterien
keine

Studienteilnehmende Mindestalter
18 Jahr(e)

Indikation
ALL - Akute lymphatische Leukämie

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinikum Köln

Einschlusskriterien
- Age 18-60 for the main trial cohort
- Age ≥ 61 years and eligible for AVD as determined by CIRS-G score and investigator for the exploratory cohort
- First diagnosis of treatment-naïve cHL
- Early-stage unfavorable disease (i.e. stage IA, IB and IIA with risk factors a-d, stage IIB with risk factors c-d):
1.) large mediastinal mass
2.) extranodal lesion(s)
3.) elevated erythrocyte sedimentation rate
4.) ≥ 3 nodal areas

Ausschlusskriterien
- Presence of nodular-lymphocyte predominant Hodgkin lymphoma, grey-zone lymphoma and/or central nervous system involvement of lymphoma

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
HD - Hodgkin Lymphom

Medizinischer Befund
Classical Hodgkin Lymphoma

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

AbbVie Deutschland GmbH & Co.KG

Einschlusskriterien
1. Subjects must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
2. Adult individuals, at least 18 years old.
3. Laboratory values meeting the following criteria within the screening period prior to the first dose of study drug:
- Adequate marrow function independent of growth factor or transfusion support within
2 weeks of Screening as follows, unless cytopenia is due to marrow involvement of CLL:
- Absolute neutrophil count (ANC) = 1.0 × 109/L
- Platelet counts = 30 x 109/L without any of the following:
- Transfusion support within 14 days of screening;
- Evidence of mucosal bleeding;
- Known history of major bleeding episode within 3 months of screening;
In cases of thrombocytopenia clearly due to marrow involvement, the platelet count should be = 10 × 109/L; the study Therapeutic Area Medical Director (TA MD) should be informed before enrollment.
- Serum alanine aminotransferase (ALT) = 2 x upper limit of normal (ULN), serum aspartate aminotransferase = 2 × ULN, and bilirubin = 2 × ULN, unless the subject has documented Gilbert's Syndrome;
- Creatinine clearance = 30 ml/min; calculated by the Cockcroft-Gault formula.
- Total hemoglobin = 8 g/dL, unless anemia is due to CLL (per discretion of the Investigator).
4. Are willing and able to comply with procedures required in this protocol.
5. Life expectancy > 6 months.
6. Documented diagnosis of CLL that requires retreatment according to iwCLL criteria.14
7. Previously completed venetoclax + anti-CD20 antibody ± X (where X is any additional drug) regimen as 1L fixed duration therapy and achieved documented response, defined as CR, CRi, PR, or nPR.
- Subjects who stopped 1L therapy earlier but completed at least 9 months of therapy and had a documented clinical response may be eligible based on the investigator's discretion.
- In Cohort 1, a maximum of approximately 20 subjects who previously received rituximab in 1L may be enrolled; in Cohort 2, there is no maximum number of subjects who previously received rituximab.
8. Patients who will not receive approved second-line therapies as assessed by the investigator and patient preference may be eligible for the study.
9. a) For Cohort 1: More than 24 months between the last dose of venetoclax and progression requiring treatment after completion of 1L venetoclax + anti-CD20 antibody ± X treatment;
b) for Cohort 2: 12- 24 months between the last dose of venetoclax and progression requiring treatment after completion of 1L venetoclax + anti-CD20 antibody ± X treatment.
10. Subject has not received an intervening treatment for CLL after completing previous treatment with venetoclax + anti-CD20 antibody ± X.
11. Subject has no contraindication for all available uric acid reducing agents.
12. No known central nervous system involvement.
13. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

Ausschlusskriterien
see Protocol

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
CLL - Chronische lymphatische Leukämie

Medizinischer Befund
Rezidivierende chronisch lymphatische Leukämie

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Thomas Schroeder

+49 (0)201 723-82530
thomas.schroeder@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

MEDAC, medac Gesellschaft für klinische Spezialpräparate mbH, Hamburg

Einschlusskriterien
1. Jene, die AML oder MDS haben und sich einer ersten allogenen HSZT unterziehen.
2. Jene, die einen passenden verwandten, passenden nicht verwandten oder haploidentischen Spender zur Verfügung haben.
3. Erwachsene beiderlei Geschlechts im Alter von 18 bis 70 Jahren.
4. Karnofsky-Index von > 60%.
5. Jene, die eine schriftliche Patienteninformation und Einwilligungserklärung abgegeben haben.
6. Jene, die eine angemessene Herzfunktion vorweisen, z. B. linksventrikuläre Ejektionsfraktion von > 40 %, entsprechend durch Multi-Gated Acquisition (MUGA) oder durch Echokardiographie beurteilt; und ein Fridericia-korrigiertes QTc (QTcF)-Intervall von < 470 ms aufweisen.
7. Jene, die bereit sind, während der Behandlung und für mindestens 6 Monate nach der Verwendung einer hochwirksamen Methode der Empfängnisverhütung wie Kondome, Implantate, Injektionen, kombinierte orale Kontrazeptiva, Intrauterinpessaren, sexuelle Abstinenz oder Vasektomie zuzustimmen, wenn es sich um gebärfähige Frauen (definiert gemäß den Richtlinien der Clinical Trials Facilitation and Coordination Group als fruchtbare Frau, nach der Menarche und bis zur Postmenopause, sofern nicht dauerhaft steril) und reproduktionsfähige Männer handelt.
8. Gebärfähige Frauen, die einen negativen Schwangerschaftstest vorweisen.

Ausschlusskriterien
Ausschlusskriterien: Teilnehmer, die eines der folgenden Ausschlusskriterien erfüllen, werden nicht für die Aufnahme in die Studie berücksichtigt:
1. Teilnehmer, die innerhalb von 3 Wochen vor dem geplanten Tag -7 als nicht für eine allogene HSZT geeignet angesehen werden, z. B. aufgrund einer schweren Begleiterkrankung:
- Teilnehmer, die eine mittelschwere oder schwere Nierenfunktionsstörung haben, z. B. Dialysepatienten, Nierentransplantationen in der Vorgeschichte, oder eine errechnete Kreatinin-Clearance (Cockcroft-Gault Formel) von < 60 ml/min haben. (Siehe im Protokoll Sektion 3.5.2.1 für die Berechnungs Details)
- Teilnehmer mit schwerwiegender Lungenfunktionsstörung, Diffusionskapazität der Lunge für Kohlenmonoxid (DLCOSB [Hämoglobin-adjustiert]) oder forcierter Exspirationsfluss (FEV1) von < 50 % oder schwere Dyspnoe im Ruhezustand oder Notwendigkeit einer Sauerstoffergänzung.
- Teilnehmer, die schwere Leberfunktionsstörung haben, angezeigt durch Hyperbilirubinämie > 3 x ONG oder Alanin-Aminotransferase (ALT) oder Aspartat-Aminotransferase (AST) > 5 x ONG.
- Teilnehmer, bei denen eine Behandlung mit Anti-Thymozyten-Globulin (ATG) während der Dauer der Treosulfan-Behandlung geplant ist.
2. Teilnehmer, die eine bekannte koronare Herzkrankheit, einen Myokardinfarkt in der Vorgeschichte, Herzfunktionsstörungen, einschließlich Kardiomyopathien, Herzinsuffizienz (New York Heart Association Klasse II und höher) und Herzrhythmusstörungen (einschließlich paroxysmalem und permanentem Vorhofflimmern), interventrikuläre Leitungsverzögerung und / oder Schenkelblock (QRS-Dauer > 120 ms) aufweisen.
3. Teilnehmer, die eine deutliche Verlängerung des QT/QTc-Intervalls zu zu Beginn der Studie (z. B. wiederholte Demonstration eines QTc-Intervalls > 450 ms) aufweisen.
4. Teilnehmer mit Vorgeschichte zusätzlicher Risikofaktoren für Torsades de Pointes (z. B. Herzinsuffizienz, Hypokaliämie, Long-QT-Syndrom in der Familienanamnese).
5. Teilnehmer, die Begleitmedikamente verwenden, von denen bekannt ist, dass sie das QT/QTc-Intervall verlängern (wie auf www.crediblemeds.org aufgeführt).
6. Teilnehmer, die eine aktive maligne Beteiligung des zentralen Nervensystems aufweisen.
7. Teilnehmer, die HIV-positiv sind oder eine aktive, nicht kontrollierte Infektionskrankheit in Behandlung haben, einschließlich Pilzinfektion, aktive virale Leberinfektion und bekannte Virusinfektion mit Coronavirus 2 (SARS-CoV-2) mit schwerem akuten respiratorischen Syndrom während der 6 Monate vor der Aufnahme.
8. Teilnehmer, die zuvor eine allogene HSZT hatten.
9. Teilnehmer, die Pleuraerguss oder Aszites von > 1,0 l haben.
10. Teilnehmer, die schwanger sind oder sich in der Stillzeit befinden.
11. Teilnehmer, die unkontrollierte oder schwere interkurrente Erkrankungen haben.
12. Teilnehmer, die eine bekannte Überempfindlichkeit gegen Treosulfan, Fludarabin und / oder verwandte Inhaltsstoffe haben.
13. Teilnehmer, die innerhalb von 4 Wochen vor Tag -7 an einer anderen experimentellen Arzneimittelstudie teilnehmen (außer denen für COVID-19-Impfstoffe). Diese Ausnahme dient der Wahrung der Interessen des Teilnehmers, da diese Bevölkerungsgruppe einem hohen Risiko für COVID-19-Komplikationen ausgesetzt ist, wenn die Krankheit auftritt. Einzelheiten zum COVID-19-Impfstoff (einschließlich Impfstoffname, Charge und Hersteller, Dosis, Datum der Verabreichung und ob der rechte oder linke Arm injiziert wurde) sollten als Begleitmedikation erfasst werden, um eine bessere Beurteilung der Gesamtwirkung der COVID-19-Impfung zu ermöglichen zu onkologischen Studienergebnissen.
14. Teilnehmer, die nicht kooperatives Verhalten oder Nichteinhaltung zeigen.
15. Teilnehmer, die psychiatrische Erkrankungen haben, die die Fähigkeit beeinträchtigen könnten, eine Patienteninformation und Einwilligungserklärung abzugeben.
16. Jede Kontraindikation für Treosulfan und/oder Fludarabin (wie in der aktuellen Version der Zusammenfassung der Merkmale des Arzneimittels [SmPC] angegeben).

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
70 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
MDS - Myelodysplastisches Syndrom, AML - Akute myeloische Leukämie

Institute
Klinik für Hämatologie und Stammzelltransplantation, Klinik für Kinderheilkunde III, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Thomas Schroeder

+49 (0)201 723-82530
thomas.schroeder@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

MEDAC, medac Gesellschaft für klinische Spezialpräparate mbH, Hamburg

Einschlusskriterien
- Subject had a previous allogeneic HSCT as indicated for malignant or non-malignant haematological disease, irrespective of human leukocyte antigen match.
- Subject has been clinically diagnosed with Grade II to IV aGvHD at the Screening Visit.
- Subject has experienced failure of previous first line aGvHD treatment (ie, SR aGvHD), defined as:
a. aGvHD progression within 3 to 5 days of therapy onset with ? 2 mg/kg/day of prednisone equivalent or
b. failure to improve within 5 to 7 days of treatment initiation with ? 2 mg/kg/day of prednisone equivalent or
c. incomplete response after > 28 days of immunosuppressive treatment including at least 5 days with ? 2 mg/kg/day of prednisone equivalent.
- Male or female subject who is ? 12 years of age and ? 15 kg at the Screening Visit.
- Subject has an estimated life expectancy > 28 days at the Screening Visit (compliance to be re-confirmed at the Baseline Visit).
- Subject, if female and of childbearing potential, agrees to use a highly effective contraceptive measure starting at the Screening Visit and continuing throughout the entire trial period. The definition of women of childbearing potential (WOCBP) and a complete list of highly effective contraceptive measures are included in an appendix to the protocol.
- Subject, if a fertile male, agrees to sexual abstinence or to use a condom during sexual activity with their female partner of childbearing potential or pregnant partner. Additionally, if their partner is a WOCBP, then their partner has to use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period. The definition of fertile men and a complete list of highly effective contraceptive measures are included in an appendix to the protocol.
- Subject or parent(s) / legal guardian(s) have read, understood, and signed the informed consent form (and informed assent form, if applicable) according to national regulations.

Ausschlusskriterien
- Subject has overt relapse or progression or persistence of the underlying disease at the Screening Visit.
- Subject has received the last HSCT for a solid tumour disease.
- Subject has GvHD overlap syndrome at the Screening Visit.
- Subject has received systemic first line treatment for aGvHD other than steroids and a prophylaxis with other than calcineurin inhibitors, anti thymocyte globulin (ATG), mycophenolate mofetil (MMF), methotrexate (MTX), and or cyclophosphamide before the Screening Visit (compliance
to be re-confirmed at the Baseline Visit).
- Subject has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit.
- Subject has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening
Visit (compliance to be confirmed for the period between the Screening Visit and the Baseline Visit at the Baseline Visit).

Studienteilnehmende Mindestalter
12 Jahr(e)

Geschlecht
Männlich

Indikation
KIK-Onko

Medizinischer Befund
Steroid refractory Acute Graft versus host Disease

MedDRA Term
Acute graft versus host disease

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Johannes Gutenberg-Universität Mainz

Einschlusskriterien
- Histologically confirmed diagnosis of MCL according to WHO classification
- previously untreated stage II-IV (Ann Arbor)
- ≥ 60 years and not suitable for autologous SCT
- At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
- ECOG performance status ≤ 2

The following laboratory values at screening (unless related to MCL):
- Absolute neutrophil count (ANC) ≥ 1000 cells/μL
- Platelets ≥75.000 cells/μL
- Transaminases (AST and ALT) ≤3 x ULN
- Total bilirubin ≤ 2 x ULN unless other reason known (Gilbert-Meulengracht-Syndrome)
- Creatinine ≤ 2 mg/dL or eGFR ≥ 50 mL/min
- Written informed consent form according to ICH/EU GCP and national regulations
- Sexually active men with female partners of child-bearing potential potential must agree to use highly effective contraceptives

Ausschlusskriterien
- Major surgery within 4 weeks prior to first dose
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon)
- History of stroke or intracranial hemorrhage within 6 months prior to first dose
- Treatment with strong or moderate CYP3A4/5 inhibitors/inducers within 7 days before first dose and during Venetoclax and Ibrutinib intake
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk
- Vaccinated with live, attenuated vaccines within 4 weeks prior to first dose
- Known CNS involvement of MCL
- Known bleeding disorder (e.g. von Willebrand disease; hemophilia)

Serious concomitant disease interfering with a regular therapy according to the study protocol:
- Cardiac (Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below LLN)
- Pulmonary (e.g. chronic lung disease with hypoxemia, e.g. DLCO = 65% or FEV1 = 65%)
- Endocrinological (e.g. severe, not sufficiently controlled diabetes mellitus)
- Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test)

Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer, Prostate cancer in remission with PSA within normal range or in situ uterine cervix cancer.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
MCL - Mantelzelllymphom

Medizinischer Befund
Mantle Cell Lymphoma

MedDRA Term
Mantle cell lymphoma NOS

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Joachim Göthert

+49 (0)201 723-82530
joachim.goethert@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

MSD Merck Sharp & Dohme LLC

Einschlusskriterien
1. Based on the WHO diagnostic criteria for myeloproliferative neoplasms (Appendix 8),
has a diagnosis of ET and an indication for cytoreductive therapy. Indications for
cytoreductive therapy include:
• High-risk patients (history of thrombosis at any age; or age >60 years with JAK2
V617F mutation),
• Acquired VWD and/or disease-related major bleeding,
• Splenomegaly,
• Progressive thrombocytosis and/or leukocytosis,
• Disease-related symptoms (eg, pruritis, fatigue, night sweats), and
• Vasomotor/microvascular disturbances not responsive to ASA (eg, erythromelalgia,
headaches/chest pain).
2. Has a bone marrow fibrosis score of Grade 0 or Grade 1, as per a modified version of the
European Consensus Criteria for Grading Myelofibrosis (Appendix 10).
3. Has received no prior cytoreductive treatment for their ET.
4. Has a platelet count of >450 × 109/L (450k/µL) assessed up to 72 hours before first dose
of study intervention.
5. Has an ANC =0.75 × 109/L assessed up to 72 hours before first dose of study
intervention.
6. Has a life expectancy of >52 weeks in the opinion of the investigator.

Ausschlusskriterien
1. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to any study intervention and/or their excipients, or to drugs chemically related to bomedemstat or LSDi (ie, MAOIs) that contraindicates participation.
2. History of any illness/impairment of gastrointestinal function that might interfere with drug absorption (eg, chronic diarrhea or history of gastric bypass surgery), confound the study results or pose an additional risk to the patient by participation in the study.
3. Evidence at the time of Screening of increased risk of bleeding due to one of the
following:
• History of severe thrombocytopenia or platelet dysfunction unrelated to a
myeloproliferative disorder or its treatment
• Known hereditary bleeding disorder (eg, dysfibrinogenemia, factor IX deficiency,
hemophilia, VWD, fibrinogen deficiency, or other clotting factor deficiency)
• Active or chronic bleeding within 8 weeks prior to randomization
• An autoimmune disorder causing bleeding
4. History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
5. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ET - Essentielle Thrombozythämie

Medizinischer Befund
Essential Thrombocythemia

Institut
Klinik für Hämatologie und Stammzelltransplantation

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

+49 (0)201 723-82530
alexander.roeth@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
Inclusion Criteria - Double blind period1. Male or female =18 years of age.2. Diagnosed with active primary or secondary wAIHA, defined as having all of the following:a.Hemoglobin concentration <9 g/dL or <10 g/dL if symptomatic or on corticosteroids/immunosuppressants ANDb.Signs of hemolysis, defined as: lactate dehydrogenase (LDH) levelsabove the upper limit of normal (ULN), or haptoglobin below the lower limit of normal, or indirect bilirubin above the ULN ANDc.Serological evidence of anti-erythrocyte antibodies associated with a DAT that is either positive for IgG only or is positive for IgG andC3d (fragment of the third component of complement) at screening.3.Has been diagnosed with wAIHA for at least 3 months, and currently receiving or has previously received treatment for wAIHA (treatment naive patients not eligible)4.If on corticosteroids, the dose must be stable for at least 14days prior to randomization.5.If currently receiving immunosuppressants, treatment must be stablefor 30 days prior to Screening. Allowed concomitantimmunosuppressants are azathioprine, mycophenolatemofetil/mycophenolic acid, cyclosporine, cyclophosphamide.6.Have a platelet count =30 × 109/L.7.Have a negative QuantiFERON®-TB Gold test.8.Patients who have undergone splenectomy must be at least 3 months post resection prior to screening and must be vaccinated as per the United States Center for Disease Control and Prevention (CDC) annual Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States9.Patients with other autoimmune disease (eg, systemic lupuserythematosus or rheumatoid arthritis) or lymphoproliferative disorders may be eligible if they are stable (no changes in concomitant diseaserelated medications and severity of disease for at least 3 months prior to screening). Patients with lymphoproliferative disease must have a low grade, be stable and be, in the opinion of the Investigator, unlikely to require chemotherapy or monoclonal antibody therapy during the study. Patients requiring change of treatment or new treatment (but not rescue therapy for wAIHA) during the study will be terminated from the study10.Have sufficient venous access to allow drug administration by IVinfusion and blood sampling as per the protocol.11.Women of childbearing potential, defined as women physiologically capable of becoming pregnant, must have a negativeserum pregnancy test at screening and a negative urine pregnancy test at Baseline. Menopausal women must have an elevated serumfolliclestimulating hormone (FSH) level at Screening; if the FSH is notelevated, they are considered to be of childbearing potential and must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Baseline to be eligible.12.Women of childbearing potential (including menopausal women who do not have elevated FSH) must agree to remain totally abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a reliable and highly effective method of contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive used in combination with an additional barrier method) during the studyand for 30 days after the last study treatment.Note: For the Czech Republic only, condom plus diaphragm, condom plus spermicide, and diaphragm plus spermicide are not considered highly effective methods of contraception.13.Male patients must agree to remain totally abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a reliable and highly effective method of contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive used in combination with an additional barrier method) to avoid pregnancy of the patient's partner(s) during the study and for 100 days following the last study treatment, unless the patient provides documentation of a vasectomy at least 6 months prior to Screening. Male patients must also abstain from sperm donation during the study and for 100 days followingthe last treatment.14.Are able to understand and voluntarily provide written informedconsent to participate in the study and comply with all study procedures.Inclusion criteria-Open-Label Extension1.Have completed the double-blind period (through Week 24), or have required rescue therapy after Week 4 of the double-blind period, or failed to demonstrate an increase from baseline in Hgb of at least 1 g/dL at or after Week 16 of the double-blind period.2.Are able to understand and voluntarily provide written informedconsent to participate in the OLE period and comply with all studyprocedures.Inclusion Criteria #6, #9, #11, #12, and #13 from the Double-blind Period (Protocol Section 4.2.1) also apply to enrollment in the OLE

Ausschlusskriterien
Exclusion Criteria - Double blind period1. Are currently taking IgG Fc-related protein therapeutics2.Have received a transfusion within 30 days prior to randomization.3.Have any other associated cause of hereditary or acquired hemolytic anemia.4.Have received rituximab within 3 months prior to screening.5.Have received IVIg within 6 weeks prior to screening.6.Have cold antibody AIHA, cold agglutinin syndrome, mixed type (ie,warm and cold) AIHA, or paroxysmal cold hemoglobinuria.7.Have a severe infection (eg, pneumonia, biliary tract infection,diverticulitis, Clostridium difficile infection) that requires parenteralanti-infectives and/or hospitalization, and/or is assessed asserious/clinically significant by the Investigator, within 8 weeks prior to screening. Any patient with an infection requiring oral antiinfectives (eg, sinusitis, bronchitis, uncomplicated urinary tract infection) within 4 weeks prior to screening will be excluded.8.Have a chronic infection (eg, bronchiectasis, chronic osteomyelitis,chronic pyelonephritis) or require chronic treatment with anti-infectives (eg, antibiotics, antivirals).9.Have received a live vaccine within 3 months prior to screening, orhave a known need to receive a live vaccine during the study or within at least 3 months after the last dose of study drug.10. Have any confirmed or suspected clinical immunodeficiencysyndrome not related to treatment of his/her wAIHA, or has a familyhistory of congenital or hereditary immunodeficiency unless confirmed absent in the patient.11.Have a known history of, or positive test result for humanimmunodeficiency virus-1 (HIV 1) and HIV 2 antibodies, hepatitis B virus (HBV core antigen), or hepatitis C virus (HCV) at screening.Note: Patients with past HCV may be included in the study if they have a documented negative HCV ribonucleic acid level in the serum at 12 weeks or longer after the completion of HCV therapy and at screening. Patients with spontaneous resolution of HCV (as confirmed by specialist) may be included in the study if they demonstrate a negative serum HCV ribonucleic acid level12.Are currently breastfeeding, pregnant, intend to become pregnantduring the study, or are planning egg donation during the study orwithin 30 days after the last dose of study drug.13.Have current alcohol/substance abuse/dependence, a history ofalcohol/substance abuse/dependence within the 12 months prior toscreening, or, in the Investigator's opinion, show evidence of ongoingalcohol/substance abuse/dependence.14.Are currently participating in another interventional clinical trial or have received any investigational drug within the past 3 months prior to screening.15.Have had any major surgery within 3 months prior to screening orhave plans for or have been scheduled for any elective surgery or major dental procedure during the study.16.Have a history of a major organ transplant (eg, heart, lung, kidney,liver), or hematopoietic stem cell/marrow transplant.17.Have a history of severe and/or uncontrolled hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric,neurological, or musculoskeletal disorder, hypertension, or any othermedical or uncontrolled autoimmune disorder that, in the opinion of the Investigator, might interfere with the patient's full participation in the study, or might jeopardize the safety of the patient or the validity of the study results.18.Received treatment for non-lymphoid malignancy within 1 year prior to screening, with the exceptions of properly treated basal or squamous cell carcinoma of the skin or properly treated carcinoma in situ of the cervix.19.Have a hypersensitivity to nipocalimab or any constituent of the study drug solution.20.Have had a prior severe therapeutic drug reaction that included hock or severe hypersensitivity.Exclusion Criteria - Opel Label Extension1. Met any of the stopping criteria (see Section 6.4.1 of the protocol) or discontinued study drug during the double-blind period due totreatment-related AE.2. Currently have a serious or clinically significant infection (eg,pneumonia, biliary tract infection, diverticulitis, C. difficile infection)requiring parenteral anti-infectives and/or hospitalization.The following exclusion criteria from the Double-blind Period (ProtocolSection 4.2.2) also apply to enrollment in the OLE: Exclusion Criteria #8and #19.

Geschlecht
Männlich, Weiblich

Indikation
Anämie

Medizinischer Befund
Adults with Warm Autoimmune Hemolytic Anemia

MedDRA Term
Anemia hemolytic autoimmune (NOS)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Joachim Göthert

+49 (0)201 723-82530
joachim.goethert@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinikum RWTH Aachen

Indikation
MPN - Myeloproliferative Neoplasie

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universität Köln

Einschlusskriterien
- Patients aged 18-69 years with ECOG PS ≥2 or ≥70 years ineligible for HCT-ASCT as per investigators discretion
- Previously untreated, histologically (or cytologically) confirmed diagnosis of primary B-cell lymphoma of the central nervous system (PCNSL) by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
- At least one measurable lesion
- Adequate organ function:
-- Adequate kidney function, defined as:
-- Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 60 ml/min
-- Adequate hepatic function, defined as:
-- ALAT and ASAT ≤ 5 ULN
-- Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease)
-- Adequate bone marrow function, defined as:
-- White blood cell (WBC) count ≥ 3000/µL or absolute neutrophil count (ANC) ≥ 1000/µL
-- Platelets ≥ 50.000/µL
-- Hemoglobin > 8.0 g/dl
--Adequate cardiac function, defined as:
-- Cardiac ejection fraction ≥ 40%
-- Adequate pulmonary function as per investigators discretion
- Written, signed, and dated informed consent must be obtained prior to participation in the study
- Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods.

Ausschlusskriterien
- Prior treatment for PCNSL with the exception of a pre-phase treatment comprising steroid treatment and / or single application of rituximab 375 mg/m2 and methotrexate 3.5 g/m2
- Systemic lymphoma manifestation outside the CNS
- Diagnosis of previous Non-Hodgkin lymphoma at any time
- Primary vitreoretinal or leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord
- HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR
- Previous or concurrent malignancies with the following exceptions:
-- Surgically cured carcinoma in-situ
-- Other kinds of cancer without evidence of disease for at least 5 years
- Hypersensitivity to study treatment or any component of the formulation
- Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR
- Congenital or acquired immunodeficiency including previous organ transplantation
- Pregnant or nursing (lactating) women and women who are not confirmed to be menopausal / post-menopausal.
- Patient's lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his / her own wishes correspondingly
- Non-compliance, e.g. due to
-- Drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
-- Refusal of blood products during treatment
-- Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
- Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
69 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
Primary Central Nervous System Lymphoma (PCNSL)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

+49 (0)201 723-82530
alexander.roeth@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Klinikum Stuttgart

Einschlusskriterien
1. Immunkompetente Patienten und Patientinnen mit Erstdiagnose eines primären B-Zell- Lymphoms (DLBCL) des zentralen Nervensystems
2. Patienten und Patientinnen Alter 18-65 Jahre unabhängig vom ECOG oder 66-70 Jahre mit ECOG Performance Status ≤ 2
3. Histologisch oder zytologisch gesicherte Diagnose eines primären B-Zell-Lymphoms des zentralen Nervensystems durch den lokalen Pathologen. Diagnosensicherung mittels stereotaktischer oder offener Biopsie, Liquorzytologie oder Vitrektomie
4. Krankheit ausschließlich lokalisiert in ZNS, Liquor oder den Hirnnerven.
5. Mindestens eine messbare Läsion
6. Patienten ohne Vorbehandlung (eine bereits erfolgte oder noch andauernde Behandlung mit Steroiden ist erlaubt)
7. Unterzeichnung der Einwilligungserklärung entsprechend den internationalen Richtlinien und der nationalen Gesetzgebung durch den Patienten oder einen autorisierten gesetzlichen Vertreter – für den Fall, dass der Patient krankheitsbedingt nicht in der Lage dazu ist.
8. Die Fähigkeit, die Art der Studie und deren Inhalte zu verstehen
9. Sexuell aktive Patienten und Patientinnen im fortpflanzungs-fähigen Alter, die zugestimmt haben, während Ihrer gesamten Studienteilnahme adäquat zu verhüten

Ausschlusskriterien
1. Kongenitale oder erworbene Immunschwäche einschließlich HIV-Infektion und Organtranplantationen in der Vergangenheit.
2. Systemische Lymphom-Manifestation (außerhalb des ZNS)
3. Isoliertes okuläres Lymphom ohne Manifestation im Hirnparenchym oder im Rückenmark
4. Andere bösartige Erkrankungen; ausgenommen sind chirurgisch entfernte Karzinome in situ der Zervix, Karzinome der Haut und andere bösartige Tumoren, die sich seit mindestens 5 Jahren in kompletter Remission befinden.
5. Diagnostiziertes Non-Hodgkin Lymphom in der Vergangenheit
6. Inadäquate renale Funktion (Kreatinin-Clearance < 60 ml/min).
7. Inadequates Knochenmark, inadäquate kardiale Leistung, inadäquate Leber- oder Lungenfunktion gemäß Einschätzung Prüfer/Prüferin
8. Active hepatitis B or C Erkrankung.
9. Laufende Behandlung mit anderen Studienmedikamenten oder Teilnahme an einer klinischen Studie innerhalb der letzten 30 Tage vor Beginn dieser Studie.
10. Flüssigkeitsansammlung im 3. Raum > 500 ml.
11. Überempfindlichkeit gegenüber der Studienmedikation oder einen anderen Bestandteil der Behandlung.
12. Einnahme von Medikamenten, die mit großer Wahrscheinlichkeit zu Wechselwirkungen mit der Studienmedikation führen
13. Bekannter oder anhaltender Missbrauch von Arzneimitteln, Drogen oder Alkohol
14. Nicht geschäftsfähiger Patient ,der Art, Bedeutung und Konsequenzen der Studie nicht erfassen und verstehen kann und keinen gesetzlichen Betreuer hat.
15. Teilnahme an der Vorgängerstudie Matrix
16. Personen, die sich in einem Abhängigkeitsverhältnis zum Sponsor und/oder Prüfarzt/Prüfärztin befinden
17. Jeglicher familiärer, soziologischer oder geographischer Umstand, der potentiell die ordnungsgemäße protokollgerechte Durchführung der Studie und der Nachbeobachtung gefährdet
18. Bestehende oder geplante Schwangerschaft, Stillzeit
19. Geschlechtsreife Patienten, die sich weigern, für die Dauer der Studienteilnahme Verhütungsmittel zu verwenden: Intrauterinpassar; Hormonverhütung in Verbindung mit einer mechanischen Verhütungsmethode

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
ZNS - Lymphom mit Befall des zentralen Nervensystems

Medizinischer Befund
Primäres diffuses großes B-Zell-Lymphom (DLBCL) des zentralen Nervensystems ist eine seltene Erkrankung der zerebalen Parenchyma, Leptomeninges, der Augen oder des Rückenmarks. Sie macht 4-6% aller Non-Hodgkin Lymphome (NHL) und 3-4% aller primären Hirntumore aus. Die Inzidenz von PZNSL ist in den vergangenen 30 Jahren angestiegen vor allem bei immunkompeten Patienten. Die durchschnittliche Überlebensrate bei unbehandelten Patienten liegt bei 3 Monaten.

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinikum Köln

Einschlusskriterien
Histologically confirmed first relapse of cHL or primary refractory cHL

4.1 INCLUSION CRITERIA
Potential participants are eligible to be enrolled in the clinical trial only if all of the following criteria apply:
1. Histologically confirmed first relapse of cHL or primary refractory cHL (primary refractory = no response to first-line therapy or recurrence within 3 months after end of first-line therapy)

2. No previous treatment for r/r HL

3. Patient is considered to be eligible for autologous stem cell transplantation by the investigator

4. Age ≥18 and <65 years on the day of signing the patient information and informed consent form (ICF)

5. Written informed consent for the clinical trial provided by the participant

6. Agreement of patient to use of their personal data and tissue material for the clinical trial, with due regard for data protection

7. Presence of measurable disease - Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of enrollment.

9. Estimated life expectancy > 3 months

10. A female participant is eligible to participate if she is not pregnant (see 12.1.4), not breastfeeding, and either
a.) Not a woman of childbearing potential (WOCBP) as defined in 12.1.4
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in 12.1.4 during the treatment period and for at least 6 months after the last dose of trial treatment.

11. A male participant must agree to use contraception as detailed in 12.1.4 of this protocol during the treatment period and for at least 6 months after the last dose of trial treatment and refrain from donating sperm during this period.

Ausschlusskriterien
Nodular lymphocyte-predominant Hodgkin lymphoma or composite lymphoma

.2 EXCLUSION CRITERIA
Potential participants cannot be enrolled in the clinical trial if any of the following criteria apply:

1. Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or composite
lymphoma

2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40,
CD137)

3. Prior allogenic tissue or solid organ transplant

4. Severe hypersensitivity (= grade 3) to pembrolizumab and/or any of its excipients

5. History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the clinical trial, interfere with the patient’s participation
for the full duration of the clinical trial, or is not in the best interest of the subject to
participate, in the opinion of the treating investigator
including:

NEUROLOGICAL/PSYCHIATRIC DISORDERS
• Symptomatic neurologic disease compromising normal activities of daily living
or requiring medications
• Active central nervous system (CNS) metastases and/or carcinomatous
meningitis
except for / permitted to enroll are patients with:
previously treated brain metastases provided they are radiologically stable, i.e.
without evidence of progression for at least 4 weeks by repeat imaging (note
that the repeat imaging should be performed during the pre-enrollment phase),
clinically stable and without requirement of steroid treatment for at least 14 days
prior to enrollment.
• Prior cerebral injury
• Epilepsy
• Psychiatric disorders, that would interfere with cooperation with requirements
of the clinical trial

CARDIAC DISORDERS
• History of one or more of the following within 6 months prior to enrollment:
o Myocardial infarction, or
o Unstable symptomatic ischemic heart disease, or
o Thromboembolic events (e.g. deep vein thrombosis, pulmonary
embolism, or symptomatic cerbrovascular events), or
o Any other serious cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy), that, in opinion of the investigator, would potentially
interfere with the completion of treatment according to the protocol
• Ongoing arrhythmias of grade > 2,
except for / permitted to enroll are patients with:
o Chronic stable atrial fibrillation on stable anticoagulant therapy
• Left-ventricular ejection fraction < 50% (recent evidence within 6 months prior
to enrollment)
• Heart failure NYHA (New York Heart Association) III or IV
• Q-wave infarction, unless identified 6 or more months prior to first dose of trial
treatment
• QTc interval > 480 msec
• Uncontrolled hypertension > 180/100 mmHg despite appropriate medication (i.e
at least 3 different antihypertensive agents)
PULMONARY DISORDERS
• Chronic obstructive pulmonary disease with global insufficiency
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids
• Active pneumonitis/interstitial lung disease or another chronic lung disease
which results in a severely impaired lung function as defined by spirometry, i.e.
forced expiratory volume in one second (FEV1) and diffusing capacity of the
lung for carbon monoxide (DLCO) (< 60% of the normal predicted value of FEV1
and DLCO)
INFECTIOUS DISORDERS
• Active infection requiring systemic therapy
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable
HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and
detectable HCV RNA) infection.
Note: Hepatitis B and C screening tests are not required unless there is a known
history of HBV and/or HCV infection and /or as mandated by local health
authority
CRITERIA FOR ENROLLMENT - EXCLUSION CRITERIA
Confidential GHSG – Pembro-CORE Pilot Trial Protocol V1.0 (15 May 2023) 29
• Known history of testing positive for human immunodeficiency virus (HIV) or
known acquired immunodeficiency syndrome (AIDS)
MALIGNANT DISORDERS
• Prior malignancy, other than cHL, active within the previous 5 years,
except for / permitted to enroll are subjects with locally curable cancers that
have been apparently cured, e.g.:
o Basal or squamous cell skin cancer
o Superficial bladder cancer
o Carcinoma in situ of the prostate, cervix or breast
AUTOIMMUNE DISORDERS
Active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is
allowed.
except for / permitted to enroll are subjects with:
o Vitiligo
o Type I diabetes mellitus
o Psoriasis not requiring systemic treatment
o Conditions not expected to recur in the absence of an external trigger
6. Abnormal organ function (except for HL-related disorders) reflected by the following
laboratory values obtained within 7 days prior to enrollment:
• Leukocytes = 2 x 109/L
• Neutrophils < 1.5 x 109/L
• Thrombocytes < 100 x 109/L
• Hemoglobin < 9.0 g/dL
• Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance
(CrCl) = 60 mL/min (if using the Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL
CRITERIA FOR ENROLLMENT - EXCLUSION CRITERIA
30 GHSG – Pembro-CORE Pilot Trial Protocol V1.0 (15 May 2023) Confidential
• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 3 x ULN
• Total Bilirubin < 2.5 x ULN (except subjects with Gilbert Syndrome, who can
have total bilirubin > 3.0 mg/dL)
• Fasting blood sugar > 200 mg/dL
• International normalized ratio (INR) OR prothrombin time (PT) / Activated partial
thromboplastin time (aPTT) > 1.5 × ULN
unless participant is receiving anticoagulant therapy as long as PT or aPTT is
within therapeutic range of intended use of anticoagulants
7. Diagnosis of immunodeficiency or chronic systemic steroid therapy (in dosing
exceeding 10 mg daily of prednisone equivalent) or any other form of
antineoplastic/immunosuppressive therapy within 7 days prior to enrollment
except for / permitted are:
o Adrenal replacement doses = 10 mg daily prednisone equivalents in the
absence of active autoimmune disease
o A brief course of systemic corticosteroids for prophylaxis or for treatment
of non-autoimmune conditions
o Inhaled or topical steroids

8. Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior
to enrollment
Note: Participants must have recovered from all AEs due to previous therapies to =
grade 1 or baseline. Participants with = grade 2 neuropathy may be eligible.
Participants with endocrine-related AEs Grade =2 requiring treatment or hormone
replacement may be eligible
Note: If participants had major surgery, they must have recovered adequately from the
procedure and/or any complications from the surgery prior to starting trial intervention.

9. Current or prior participation in a clinical trial of an investigational agent or use of
investigational device within 4 weeks prior to enrollment.
Note: Participants who have entered the follow-up phase of an investigational clinical
trial may participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.

10. Prior radiotherapy within 2 weeks prior to enrollment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (= 2 weeks of radiotherapy) to non-CNS disease.
CRITERIA FOR ENROLLMENT - EXCLUSION CRITERIA
Confidential GHSG – Pembro-CORE Pilot Trial Protocol V1.0 (15 May 2023) 31

11. Live vaccine or live-attenuated vaccine within 30 days prior to enrollment and while
participating in the trial.
Note: Administration of killed vaccines is allowed. Any licensed COVID-19 vaccine
(including for Emergency Use) in a particular country is allowed in the study as long
as they are mRNA vaccines, replication-incompetent adenoviral vaccines, or
inactivated vaccines. These vaccines will be treated just as any other concomitant
therapy

12. Patient’s lack of accountability and inability to appreciate the nature, meaning and
consequences of the clinical trial and to formulate his/her own wishes correspondingly

13. Non-compliance, e.g. due to
• Drug dependency or substance abuse that would interfere with cooperation with
requirements of the clinical trial
• Refusal of blood products during treatment
• Change of residence to abroad
• Any similar circumstances that appear to make protocol treatment or long-term
follow-up impossible

14. Pregnancy (for details please see 12.1.4), breastfeeding, or expecting to conceive or
father children within the projected duration of the clinical trial, starting with the preenrollment
visit through 6 months after the last dose of trial treatment

15. Patients who have a relationship of dependence or employer-employee relationship to
the sponsor or the investigator

16. Committal to an institution on judicial or official order

17. Has not adequately recovered from major surgery or has ongoing surgical
complications

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
65 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
HD - Hodgkin Lymphom

Medizinischer Befund
First-relapsed or Refractory Classical Hodgkin Lymphoma

MedDRA Term
Lymphomas Hodgkin's disease

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Andreas Hüttmann

+49 (0)201 723-82530
Andreas.Huettmann@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsmedizin Berlin

Augustenburger Platz 1
13353 Berlin

Einschlusskriterien
Alle Patienten mit PTLD

Ausschlusskriterien
keine

Studienteilnehmende Mindestalter
Jahr(e)

Studienteilnehmende Höchstalter
99 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
Posttransplantations-Lymphoproliferative Erkrankungen (PTLD)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
1. Signed informed consent, by the patient or an authorized legal guardian in case the patient is temporarily not competent due to his or her disease, obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
2. Patients of either gender aged > 18 years.
3. Body weight < 180 kg.
4. At least one measurable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesion.
5. Histologically confirmed diagnosis of relapsed or refractory primary central nervous system lymphoma (PCNSL) or histologically confirmed diagnosis of relapsed or refractory secondary central nervous system lymphoma (SCNSL) with only isolated CNS involvement (at initial diagnosis of relapse).
6. Recurrent or refractory CNSL
1. For recurrent disease, comprising new lesions or recurrent CNSL after a complete response (CR) at that site, there are no maximum number of recurrences.
2. Refractory CNSL comprises patients with non-responding CNSL (no objective response rate (ORR), no progressive disease (PD)) to frontline therapy, or progressive disease after an initial, partial response (PR).
7. Stored stem cells with at least ≥ 2 x 106 CD34+ cells/kg of body weight.
8. If sexually active female patient of childbearing potential: patient agrees to take adequate contraceptive measures during study participation and agrees to continue use of this method for the duration of the study and for six months after the last dose.
9. Female patient without childbearing potential: documented history (e.g., tubal ligation or hysterectomy) or is post-menopausal.
10. For male patient whose partner is of child-bearing potential: patient is willing to ensure that he and his partner use effective contraception during the study and for six months after 90Y-PTT treatment.
11. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
12. Confirmed presence of CXCR4 on technically evaluable tumor lesions documented by a visually CXCR4-positive [68Ga]Ga-PentixaFor positron emission tomography (PET) scan within two months prior to enrolment in the study or during Screening.
13. Blood test results as follows:
1. Absolute neutrophil count: > 1.0 x 109/L
2. Hemoglobin: ≥ 8 g/dL
3. Platelets: ≥ 75 x 109/L
4. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP): ≤ 3 x ULN (upper limit of normal)
5. Serum creatinine: ≤ 2 x ULN and Cockcroft Gault calculated glomerular filtration rate (GFR) ≥ 50 mL/min
6. Bilirubin: ≤ 3 x ULN

Ausschlusskriterien
1. Known or suspected hypersensitivity to study product(s) or related products.
2. Contraindication for contrast-enhanced magnetic resonance imaging (MRI) as set out in the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal in the body, renal insufficiency, severe claustrophobia etc.) or contraindication for the use of gadolinium contrast for MRI.
3. Previous participation in this study. Participation is defined as signed informed consent.
4. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). A pregnancy test will be performed at the start of the study for all female patients of childbearing potential (i.e., not surgically sterile or two years postmenopausal).
5. Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
6. Participation in any clinical study of an approved or non-approved investigational medicinal product (IMP) within the last 30 days (or = 5 terminal elimination half-lives of previous IMP, whichever is longer) before screening.
7. Any disorder (e.g., active infection, unstable angina pectoris, cardiac arrhythmia (excluding atrial fibrillation and atrial flutter, uncontrolled congestive heart failure), poorly controlled hypertension, poorly controlled diabetes mellitus [HbA1c = 9%], etc.) or laboratory findings, except for conditions associated with CNS lymphoma, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
8. Presence of active infection at screening, or history of serious infection within the previous six weeks. Patients with uncontrolled human immunodeficiency virus (HIV) infection as well as acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded (Note: Patients on antiretroviral therapy (ART) with controlled HIV infection (defined as sufficient ART compliance, non-measurable HIV and CD4+ T helper cells > 200/Micro Liter) may be enrolled, if considered eligible for study treatment by the investigator.).
9. SCNSL with systemic involvement.
10. Chronic use (> 21 days) of immunosuppressive drugs, e.g., steroids for systemic autoimmune disease, due to previous organ transplantation, or other clinically evident form of immunodeficiency. Patients receiving only acute treatment (less than 21 days) with corticosteroids can be included.
11. Any mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study, and/or evidence of an uncooperative attitude without designated legal representative.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
120 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ZNS - Lymphom mit Befall des zentralen Nervensystems

Medizinischer Befund
CNS Lymphoma

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

+49 (0)201 723-82530
bastian.vontresckow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Regeneron Pharmaceuticals, Inc, USA

Indikation
DLBCL - Diffuses großzelliges B-Zell-Lymphom

Medizinischer Befund
Diffuse Large B-Cell Lymphoma (DLBCL)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

+49 (0)201 723-82530
alexander.roeth@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Swedish Orphan Biovitrum AB, Schweden

Einschlusskriterien
* Patients ≥18 years of age with a documented PNH diagnosis.
* Patient started routine treatment with pegcetacoplan for PNH up to 12 months before enrollment or prescribed pegcetacoplan at enrollment. Decision to initiate treatment shall be made by the treating physician and independently from the decision to include the patient in the study.
* Patient is willing and able to provide written informed consent to participate in the study in a manner approved by the Institutional Review Board/Independent Ethics Committee and local regulations.

Ausschlusskriterien
* Enrollment in a concurrent clinical interventional study, or intake of an Investigational Medicinal Product (IMP), within three months prior to the start of the current pegcetacoplan treatment.
* Initiated current treatment with pegcetacoplan in an interventional study.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
PNH - Paroxysmale nächtliche Hämoglobinurie

Medizinischer Befund
Paroxysmal Nocturnal Hemoglobinuria

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
* Age: 16 years and older (Part A), 12 years and older (Parts B and C).
* Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with:
- Bone marrow infiltration with >/= 5% blasts
- Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
- Philadelphia positive participants are allowed in Part A if intolerant or refractory to TKIs.
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2 OR Lansky score more or equal to 50%.
The above is a summary, other inclusion criteria details may apply.

Ausschlusskriterien
* Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
* Isolated extramedullary disease relapse.
* Testicular leukemia
* History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
* History of other malignancy (with certain exceptions).
* Unresolved AEs >/= Grade 2, from prior therapies
* Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
* GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.
The above is a summary, other exclusion criteria details may apply.

Studienteilnehmende Mindestalter
12 Jahr(e)

Studienteilnehmende Höchstalter
80 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ALL - Akute lymphatische Leukämie

Medizinischer Befund
B-cell Acute Lymphoblastic Leukemia (B-ALL)

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum, WTZMS - Westdeutsches Tumorzentrum Münster

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Technische Universität Dresden

Einschlusskriterien
• Written informed consent
• Newly diagnosed AML according to the criteria of the World Health Organisation plus the following molecular or cytogenetic specifications:
o Phase I Trial - MODULE:
? t(8;21)/RUNX1-RUNX1T1 or
? inv(16) or t(16;16)/CBFB-MYH11 or
? FLT3-ITD or
? FLT3-tyrosine kinase domain (FLT3-TKD)
o Phase II Trial - MAGNOLIA
? t(8;21)/RUNX1-RUNX1T1 or
? inv(16) or t(16;16)/CBFB-MYH11
o Phase II Trial - MAGMA
? FLT3-ITD or
? FLT3-TKD
? Absence of mutations in CBF genes (i.e. t(8;21)/RUNX1-RUNX1T1 or inv(16) or t(16;16)/CBFB-MYH11)
• Male and female patients aged
o 18 - = 75 years in Phase I Trial - MODULE
o 18 - = 70 years in Phase II Trials - MAGMA and MAGNOLIA
• Eastern Cooperative Oncology Group (ECOG) Score of 0-2
• Life expectancy > 14 days
• Adequate hepatic and renal function
o alanine aminotransferase / aspartate transaminase = 2.5 x ULN
o Bilirubin < 2 x upper limits of normal
o Creatinine 40 ml/min
• White blood cell count < 30 × 10^9/L. Note: Hydroxyurea and/or a dose of 100-200 mg/m^2 cytarabine per day for up to 3 days (for emergency use for clinical stabilization) is permitted to meet this criterion.

Ausschlusskriterien
Alle Phasen:
· vorangegangene antineoplastische AML-Therapien, außer Hydroxyharnstoff,
· vorangegangene Behandlung mit Anthrazyklinen,
· ZNS-Beteiligung,
· Unkontrollierte Infektion,
· Einnahme starker Induktoren von CYP3A4/5, die nicht vor Studieneinschluss abgesetzt oder ersetzt werden können.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
AML - Akute myeloische Leukämie

Medizinischer Befund
Patienten mit neudiagnostizierter akuter myeloischer Leukämie (AML) und zytogenetischen Anomalien bzw. Fusionstranskript der Core-binding-factor-Gene (CBF) oder eine FLT3-Mutation, die für eine kurative intensive Erstlinientherapie geeignet sind

MedDRA Term
Acute myeloid leukemia

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Maher Hanoun

+49 (0)201 723-82530
maher.hanoun@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinik Carl Gustav Carus der TU Dresden, Hautklinik

Einschlusskriterien
* A signed informed consent
* Newly diagnosed CD33-positive AML with NPM1 mutation according to WHO criteria
* Age 18-70 years
* Fit for intensive chemotherapy, defined by
- ECOG performance status of 0-2
- Adequate hepatic function: ALAT/ASAT/Bilirubin = 2.5 x ULN unless considered due to leukemic organ involvement Note: Subjects with Gilbert's Syndrome may have a bilirubin > 2.5 × ULN per discussion between the investigator and Coordinating investigator.
- Adequate renal function assessed by serum creatinine = 1.5x ULN OR creatinine clearance (by Cockcroft Gault formula) = 50 mL/min
* WBC < 25 x 109/L (<25,000/µL), prior hydroxyurea is permitted to meet this criterion
* Ability to understand and the willingness to sign a written informed consent.
* Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 7 months after the last dose of study drug.
* Women of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours before first dose of study drug.

Ausschlusskriterien
* Activating FLT3 mutation
* Relapsed or refractory AML
* AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment
* Prior history of malignancy, other than MDS, unless the subject has been free of the disease for = 1 year prior to start of study treatment (exceptions are basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis clinical staging system))
* Previous treatment with HMA or venetoclax
* Previous treatment for AML except hydroxyurea
* Cumulative previous exposure to anthracyclines of > 200 mg/m^2 doxorubicin equivalents
* CNS involvement or extramedullary disease only
* Known hypersensitivity to excipients of the preparation or any agent given in association with this study including venetoclax, azacitidine, cytarabine, daunorubicin, gemtuzumab-ozogamicin, or mitoxantrone
* Known positivity for human immunodeficiency virus (HIV) and History of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (i.e. PCR undetectable viral load for hepatitis).
* Inability to swallow oral medications
* Any malabsorption condition
* Cardiovascular disability status of New York Heart Association (NYHA) Class = 2; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Note: Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
* Chronic respiratory disease that requires continuous oxygen use
* Substance abuse, medical, psychological, or social conditions that may interfere with the subject's cooperation with the requirements of the trial or evaluation of the study results
* Simultaneous participation in another interventional clinical trial
* Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of and during treatment and should be discontinued for at least 3 months after end of treatment.
* Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with an Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 7 months after the last dose of study drug unless one of the following criteria is met:
- post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH > 40 U/ml)
- postoperative (6 weeks after bilateral ovarectomy with or without hysterectomy)
- medically confirmed ovarian failure
- vasectomy Note: At present, it is not known whether the effectiveness of hormonal contraceptives is reduced by venetoclax. For this reason, women must use a barrier method in addition to hormonal contraceptive methods.
* History of clinically significant liver cirrhosis (e.g., Child-Pugh class B and C)
* Live-virus vaccines given within 28 days prior to the initiation of study treatment Note: corona vaccines are not live-virus vaccines and are excluded from this criterion.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
70 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
AML - Akute myeloische Leukämie

Medizinischer Befund
AML - Akute myeloische Leukämie

MedDRA Term
AML