Studien

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

Indikation
PNH - Paroxysmale nächtliche Hämoglobinurie

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Christina Rautenberg

+49 (0)201 723-82530
christina.rautenberg@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)

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 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

argenx BVBA, Belgien

Einschlusskriterien
• Is at least 18 years of age and the local legal age of consent for clinical studies when signing the informed consent form (ICF).
• Has documented baseline mean platelet count of <30 x 10^9/L before randomization
• Has a documented duration of primary immune thrombocytopenia (ITP) of more than 12 months on the date of informed consent form (ICF) signature.
• Has documented prior ITP treatment with at least 1 of the following treatments: corticosteroids, intravenous immunoglobulin (IVIg), anti-D immunoglobulin, thrombopoietin receptor agonist (TPO-RAs), or rituximab.
• Has documented insufficient response to a prior ITP treatment (the specific criteria can be found in the protocol).
• Has documented prior response defined as 1 platelet count of =50 × 109/L to at least 1 of the following ITP treatments in the 3 years before the date of ICF signature: prednisone, dexamethasone, other or nonspecified corticosteroids, IVIg, or anti-D immunoglobulin

Ausschlusskriterien
• Other than the indication under study, known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of ITP, confound the results of the study or put the participant at undue risk.
• Secondary ITP
• Nonimmune thrombocytopenia
• Autoimmune hemolytic anemia
• ITP-associated critical or severe bleeding The complete list of criteria can be found in the protocol.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ITP - idiopathische thrombozytopenische Purpura

Medizinischer Befund
Primary Immune Thrombocytopenia (ITP)

MedDRA Term
Idiopathic thrombocytopenic purpura

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

BeiGene Ltd., c/o BeiGene USA, Inc.

Einschlusskriterien
1. Confirmed diagnosis of CLL or SLL, requiring treatment, based on 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria.
2. Previously received treatment for CLL/SLL with both a BTKi and a BCL2i.
3. Participants with SLL must have measurable disease by computer tomography (CT)/magnetic resonance imaging (MRI)
4. Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2
5. Adequate liver function
6. Adequate blood clotting function

NOTE: Other protocol defined Inclusion criteria may apply.

Ausschlusskriterien
1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
2. Prior autologous stem cell transplant or chimeric antigen receptor-T cell therapy in the last 3 months
3. Known central nervous system involvement
4. Prior exposure to any BTK protein degraders
5. Active fungal, bacterial and/or viral infection requiring parenteral systemic therapy
6. Clinically significant cardiovascular disease

NOTE: Other protocol defined Exclusion criteria may apply.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
CLL - Chronische lymphatische Leukämie

Medizinischer Befund
CLL\nChronic Lymphocytic Leukemia

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

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

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)

Dr. med. Amelie Boquoi

+49 (0)201 723-82530
amelie.boquoi@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Astra Zeneca AB, Schweden

Einschlusskriterien
• Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place.
• Eastern Cooperative Oncology group (ECOG) performance status of = 2.
• Documentation of Multiple Myeloma (MM) as defined by International Myeloma Working Group (IMWG) Diagnostic Criteria for Multiple Myeloma. Site should ensure that Multiple Myeloma diagnosis is confirmed in accordance with the IMWG Diagnostic Criteria.
• Participants must have one or more of the following measurable disease criteria:
1. Serum M-protein level = 0.5 g/dL.
2. Urine M-protein level = 200 mg/24h.
3. Serum immunoglobulin free light chain = 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Adequate organ and bone marrow function assessment at screening according to the hematological, hepatic, and renal parameters listed in the CSP.
• Participants must have received at least 3 prior lines of treatment which include a proteasome inhibitor (e.g., bortezomib), an immunomodulator (e.g., lenalidomide), and an anti-CD38 antibody (e.g., daratumumab).

Ausschlusskriterien
• Participants exhibiting clinical signs of central nervous system involvement of MM.
• Participants with known COPD, or previous history of ILD.
• Participants with known moderate or severe persistent asthma within the past 5 years, or uncontrolled asthma of any classification.
• Participants who have severe cardiovascular disease which is not adequately controlled.
• Participants who have a history of immunodeficiency disease.
• Participants with peripheral neuropathy = Grade 2.
• Primary refractory MM.
• Participants who have previously received anti-GPRC5D or MMAE-containing treatment.
• Participants who have previously received allogenic stem cell transplant, or participant has received autologous stem cell transplant within 3 months before the first dose of study intervention.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
MM - Multiples Myelom

Medizinischer Befund
Multiple Myeloma

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

Indikation
Waiha – Autoimmunhämolytische Anämie vom Wärmetyp

Medizinischer Befund
warm autoimmune hemolytic anemia

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 für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Alexander Carpinteiro

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

Hufelandstr 55
45147 Essen

Einschlusskriterien
• Histologic diagnosis of AL amyloidosis and typed with immunohistochemistry/ immunofluorescence, immunoelectron microscopy, or mass spectrometry. In patients with biopsy-confirmed amyloidosis, ambiguous amyloid typing results, and cardiac involvement alone, a negative pyrophosphate (PYP) or technetium-99m (99mTc) and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD-Tc99m) bone scan is required to distinguish cardiac involvement due to AL amyloidosis from amyloid transthyretin (ATTR) amyloidosis. Data from the initial diagnosis are accepted.
• Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis, or immunohistochemistry/ immunofluorescence/ immunoelectron microscopy/ mass spectrometry of amyloid deposits must provide clear evidence of ? or ? light chains in patients who present with peripheral neuropathy or heart as the dominant organ involvement. Data from the initial diagnosis are accepted.
• Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2
• Mayo stage I-IIIA cardiac disease at Screening
• Relapsed patients must have received at least 1 line of treatment, including Dara and bortezomib. Patients must have received at least two cycles of therapy. However, patients who have received high-dose therapy with melphalan as their only therapy are also eligible.
• Measurable hematologic disease: a dFLC >20 mg/L with an abnormal ?/? ratio (with Freelite® test kits, The Binding Site) or presence of a monoclonal spike =0.5 g/dL.
• Adequate bone marrow function, without transfusion or growth factors within 5 days prior to the first drug intake (C1D1), defined as:
• Absolute neutrophils =1,000/mm3,
• Platelets =75,000/mm3,
• Hemoglobin =8.5 g/dL.
• Adequate organ function, defined as:
• Serum creatinine clearance (CKD-EPI formula) =20 mL/min,
• Serum SGPT/ALT <5.0 x Upper Limit of Normal (ULN),
• Serum total bilirubin <2.0 mg/dL or direct bilirubin =30% of the total, unless the patient has Gilbert's syndrome, where direct bilirubin should then be <2.0 mg/dL,
• Serum albumin =<2.5 gr/dl (medication to correct serum albumin levels is permitted).

Ausschlusskriterien
• Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis.
• Isolated soft-tissue involvement.
• Presence of non-AL amyloidosis.
• Previous anti-BCMA targeted therapy (including, but not limited to, bispecifics).
• Intolerance to dexamethasone that would prohibit treatment with trial therapy.
• MM diagnosed as per the International Myeloma Working Group (IMWG) criteria, with the exception of monoclonal gammopathy of unknown significance (MGUS) or smoldering Myeloma, not requiring treatment.

Note: A MM diagnosis with a serum FLC ratio >100, as the only myeloma-defining event, does NOT constitute an exclusion.
• All hematologic malignancies, with the exception of low-risk Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms (MPNs) and low-risk myelodysplastic syndromes (MDS), not requiring treatment.
• Mayo stage IIIB cardiac disease at Screening

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
AL-Amyloidose

Medizinischer Befund
AL Amyloidosis

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

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

Westfälische Wilhelms-Universität Münster

Einschlusskriterien
• GD2-Expression auf Tumorzellen in archivierten oder neu gewonnenen Biopsien (empfohlen nach GD2-Antikörpertherapie) im zentralen Referenzlabor. GD2-Positivität ist definiert als =50 % Expression von GD2 mit einer Intensität von =2+ im Tumorgewebe unter Verwendung eines immnfluoreszenbasierten Assays für den spezifischen Nachweis von GD2 in Formalin-fixiertem, Paraffin-eingebettetem oder gefrorenem Tumorgewebe.
•Auswertbare Erkrankung basierend auf imRECIST (alle Krankheitsentitäten) oder bei diffuser Knochen-/Knochenmarkmetastasierung durch Ganzkörper-MIBG-Scan (Neuroblastom) oder Ganzkörper-FDG-PET-Scan (alle Entitäten)
• Alter =1 Jahr und <80 Jahre
• Absolute CD3+ T-Zellzahl =200/µl
• ECOG-Performance-Score von 0–2 bei Alter von >16 Jahren oder Lansky-Performance-Score von =60 bei Alter von =16 Jahren beim Screening
• Kein gebärfähiges Potenzial oder negativer Schwangerschaftstest beim Screening und vor Chemotherapie bei Frauen im gebärfähigen Alter
• Unterschriebene und datierte Einverständniserklärung/Zustimmung von Patientin/Patient und/oder Eltern vor der Durchführung eines studienspezifischen Verfahrens.

Ausschlusskriterien
Patientinnen/Patienten werden nur dann in diese Studie aufgenommen, wenn keines der folgenden Kriterien zutrifft:
• Aktive solide Metastasen des Zentralnervensystems (ZNS) oder metabolisch aktive Metastasen im Schädel mit direktem Kontakt zur Dura
• Aktuelle Autoimmunerkrankung oder Vorgeschichte einer Autoimmunerkrankung mit möglicher ZNS-Beteiligung
• Aktive klinisch signifikante ZNS-Dysfunktion (einschließlich, aber nicht beschränkt auf unkontrollierte Krampfanfälle, zerebrovaskuläre Ischämie oder Blutung, Demenz, Lähmung)
• Vorgeschichte einer zusätzlichen malignen Erkrankung außer nicht-melanozytärem Hautkrebs oder Carcinoma in situ oder seit ? 3 Jahren krankheitsfrei
• Lungenfunktion: Patienten mit vorbestehender schwerer Lungenerkrankung oder einem Sauerstoffbedarf von >28 % O2-Supplementierung oder aktiven Lungeninfiltraten im Röntgenbild
• Herzfunktion: Pädiatrische Patienten: fraktionelle Verkürzung < 28 % oder linksventrikuläre Ejektionsfraktion < 50 % laut Echokardiographie, erwachsene Patienten: linksventrikuläre Ejektionsfraktion < 50 % laut Echokardiographie
• Nierenfunktion: GFR ?29 ml/min/1,73 m2 nach CKD-EPI für Patienten ?18 Jahre oder Kreatinin-Clearance ?29 ml/min/1,73 m2 nach Schwartz-Formel für Patienten <18 Jahre
• Leberfunktion: Patientinnen/Patienten mit einem Serum-Bilirubin >3-fach oberhalb der Obergrenze des Normalwerts oder einem AST- oder ALT-Wert >5-fach oberhalb der Obergrenze des Normalwerts, es sei denn aufgrund einer Leberinfiltration durch die zugrundeliegende maligne Erkrankung nach Einschätzung des Prüfarztes
• Hämatologische Funktion: Patienten müssen einen absoluten Neutrophilen-Count (ANC) ? 500/µl und einen Thrombozytenzahl von ? 50 × 10e3/µl haben.
• Rasch fortschreitende Erkrankung, die nach Einschätzung des Prüfarztes die Fähigkeit beeinträchtigen würde, die Studientherapie abzuschließen
• Schwangere oder stillende Frauen
• Gleichzeitig oder vorangegangene Therapien:
- Hochdosis-Chemotherapie mit autologer Stammzelltransplantation oder mit Bedarf an autologem Stammzell-Rescue oder Biologika (z. B. Mifamurtid, Interferone) oder Immuncheckpoint-Inhibitoren oder Strahlentherapie oder größerer chirurgischer Eingriff innerhalb von 30 Tagen vor der Leukapherese.
- Neuroblastom-Patientinnen/Patienten mit Rezidiv nach allogener oder haploidenter Stammzelltransplantation müssen mindestens 100 Tage nach Transplantation sein, ohne Anhalt für GvHD und ohne Einnahme immunsuppressiver Substanzen für mindestens 30 Tage vor Leukapherese.
- I131 MIBG-Therapie (Neuroblastome) muss mindestens 3 Monate vor Apherese abgeschlossen sein. - GD2-spezifische Antikörpertherapie mit Dinutuximab-beta oder Naxitamab innerhalb von 40 Tagen (5 Halbwertzeiten)
- Antiproliferative Chemotherapien, epigenetische Substanzen, Antikörper-Drug-Konjugate, Antikörper gegen andere Antigene als GD2 innerhalb von 3 Wochen vor Leukapherese
- Andere immunsuppressive Substanzen als Steroide innerhalb von 14 Tagen vor der Leukapherese
- Kurz wirkende molekular zielgerichtete Wirkstoffe (Kinase-Inhibitoren) innerhalb von 7 Tagen vor der Leukapherese
- Systemische Kortikosteroide mit Ausnahme einer physiologischen Ersatzdosierung innerhalb von 7 Tagen vor der Leukapherese
- Lebendimpfstoffe innerhalb von 30 Tagen vor der Leukapherese
• Überempfindlichkeit gegen ein Medikament oder seine Inhaltsstoffe/Verunreinigungen, die während der Studienteilnahme geplant oder wahrscheinlich verabreicht werden, z. im Rahmen der obligatorischen präparativen Chemotherapie, Prämedikation zur Infusion, Notfallmedikation/Salvage-Therapien bei behandlungsbedingten Toxizitäten
• Kontraindikation für prüfungsbezogene Verfahren nach Einschätzung des Prüfarztes, z. Tumorbiopsie
• Patientinnen im gebärfähigen Alter, die ab dem Zeitpunkt der Unterzeichnung der Einwilligungserklärung und für 12 Monate nach Verabreichung des IMP nicht bereit sind, eine hochwirksame Form der Empfängnisverhütung zu praktizieren
• Männliche Patienten mit Vaterschaftspotential, die ab dem Zeitpunkt der Unterzeichnung der Einwilligungserklärung und für 12 Monate nach Verabreichung des IMP nicht bereit sind, eine hochwirksame Form der Empfängnisverhütung zu praktizieren
• Gleichzeitige Teilnahme an einer anderen interventionellen Studie, die mit dieser Studie interagieren könnte, z. CAR T-Versuche
• Zerebrale Dysfunktion, Geschäftsunfähigkeit erwachsener Patienten; Einweisung in eine Anstalt auf gerichtliche oder behördliche Anordnung

Studienteilnehmende Mindestalter
1 Jahr(e)

Indikation
Solide Tumoren

Medizinischer Befund
solid cancers\nRezidivierte oder refraktäre GD2-positive solide Tumoren

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. Thomas Schroeder

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

Hufelandstr. 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

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

GSK GmbH & Co. KG

Einschlusskriterien
1. Is age =18 years.
2. Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post-PV/ET myelofibrosis in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.
3. JAKi naïve or previously treated with either ruxolitinib or fedratinib for PMF or Post-PV/ET myelofibrosis for =90 days, or =28 days if JAKi therapy is complicated by RBC transfusion requirement of =4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma.
4. High risk, intermediate-2, or intermediate-1 risk as defined by Dynamic International Prognostic Scoring System (DIPSS) [Passamonti, 2010] or DIPSS-plus [Gangat, 2011].
5. TD defined as requiring RBC transfusion =4 units or HgB < 8 g/dL in the 8 weeks prior to the first dose of study treatment. Only transfusions given when Hgb levels are =9.5 g/dL are counted towards TD. RBC transfusions given for clinically overt bleeding, or accident/injury (as assessed by the investigator) are not counted towards TD.

Ausschlusskriterien
1. History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (e.g., uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study intervention or result in inability to swallow oral medications.
2. Participants with an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years.
3. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, gastrointestinal bleeding, or thalassemia.
4. Uncontrolled intercurrent illness:
1. Active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial);
2. Uncontrolled acute and chronic liver disease (e.g., Child-Pugh score =10) OR has current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
5. Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure =140 mmHg or diastolic blood pressure =90 mmHg, that is not resolved at the time of the first dose of study treatment.
6. Any of the following in conditions within 6 months prior to the first dose of study intervention:
1. Unstable angina pectoris; OR
2. Symptomatic congestive heart failure; OR
3. Uncontrolled cardiac arrhythmia
7. QTc interval >450 msec or QTc >480 msec for participants with bundle branch block.
8. Participants with stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to the first dose of study intervention.
9. History of porphyria.
10. Presence of peripheral neuropathy =Grade 2 per CTCAE v5.0.
11. Use of the following treatments within the time periods noted NOTE: All active anti-MF therapy must discontinue at least 1 week prior to the start of baseline MFSAF recording (Study Day -7):
1. Active anti-MF therapy within 28 days or 5 half-lives, whichever is shorter (exception is prior JAKi therapy).
2. Steroid use for the treatment of myelofibrosis is prohibited within 14 days prior to the first dose of study treatment until discontinuation of study treatment. Supportive care including steroids for non-myelofibrosis indications may be used.
3. Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of study intervention.
4. Any prior investigational agent for myelofibrosis within 4 weeks prior to the first dose of study treatment.
5. Erythropoiesis stimulating agent (ESA) within 4 weeks prior to the first dose of study treatment.
6. Splenic irradiation within 3 months prior to the first dose of study treatment.
12. Prior treatment with MMB.
13. Prior treatment with luspatercept or sotatercept.
14. Prior splenectomy.
15. Inability or unwillingness to comply with the protocol restrictions on myelofibrosis therapy and other medications prior to and during study treatment.
16. Unresolved non-hematologic toxicities from prior therapies that are >Grade 1 per CTCAE v5.0 unless otherwise specified.
17. Known positive status for human immunodeficiency virus (HIV).
18. Hepatitis A, B, or C status as defined below:
1. Chronic active or acute viral hepatitis A.
2. Active Hepatitis B infection indicated by the presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to the first dose of study intervention.
3. Positive hepatitis C antibody test result at screening or within 3 months before the first dose of study intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained.
19. Women who are already pregnant or lactating.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
MPN - Myeloproliferative Neoplasie

Medizinischer Befund
Primary Myelofibrosis\nMyelofibrosis; \nPrimary Myelofibrosis; \nPost-polycythemia Vera Myelofibrosis; \nPost-essential Thrombocythemia Myelofibrosis

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
Study Population
PNH patients with a confirmed diagnosis of PNH by flow cytometry

• Patients with PNH confirmed by flow cytometry.
• Patient and/or parent/legally authorized representative provide written informed consent/assent to participate in the registry in a manner approved by the Institutional Review Board/Independent Ethics Committee and local regulations.

Ausschlusskriterien
• Participating in an interventional PNH clinical trial.

Note: A patient included in the registry, who enrolls in an interventional PNH clinical trial during the course of the registry, will be kept in the registry but data collection will be paused in the registry during their involvement in the clinical trial/extension study. Data collection in the registry will continue after patient involvement in the clinical trial/extension study has ended or trial protocol mandated data collection ceases.

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. Bastian von Tresckow

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

Hufelandstraße 55
45147 Essen

Sponsor

Kite Pharma, Inc., USA

Einschlusskriterien
• Documented historical diagnosis of multiple myeloma (MM)
• Received 1 to 3 prior lines of antimyeloma therapy, including an immunomodulatory drug (IMiD) and an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb). A minimum of 2 consecutive cycles of an IMiD and an anti-CD38 mAb in any prior line of therapy is required. The IMiD and anti-CD38 mAb do not need to be from the same regimen in the prior line(s) of therapy.
• Documented evidence of progressive disease by IMWG criteria based on the investigator's determination on or within 12 months of the last dose of the last regimen
• Measurable disease at screening per IMWG, defined as any of the following:
o Serum M-protein level = 0.5 g/dL or urine M-protein level = 200 mg/24 hours; or
o Light chain MM without measurable disease in the serum or urine: serum free light chain = 10 mg/dL and abnormal serum free light chain ratio
• Only individuals who are candidates to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd), as determined by the investigator, should be considered for this study
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)

Note: Other protocol defined Inclusion criteria may apply.

Ausschlusskriterien
• Prior B-cell maturation antigen (BCMA)-targeted therapy
• Prior T-cell engager therapy
• Prior CAR therapy or other genetically modified T-cell therapy
• Active or prior history of central nervous system (CNS) or meningeal involvement of MM
• Cardiac atrial or cardiac ventricular MM involvement
• History of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
• Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted.
• Prior auto-SCT within 12 weeks before randomization
• Prior allogeneic stem cell transplant (allo-SCT)
• High-dose (eg, cumulative > 70 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days before randomization
• Live vaccine ? 4 weeks before randomization
• Contraindication to fludarabine or cyclophosphamide
• History of allergy or hypersensitivity to any study agent or study drug components. Individuals with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.
• Life expectancy < 12 weeks

Note: Other protocol defined Exclusion criteria may apply.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
MM - Multiples Myelom

Medizinischer Befund
Relapsed\/refractory multiple myeloma in patients who have received 1 to 3 prior lines of therapy and have been exposed to both an immunomodulatory drug and an anti-CD38 monoclonal antibody

MedDRA Term
Relapsed\/refractory multiple myeloma

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

MaaT Pharma, France

Einschlusskriterien
• Age = 50 years old
• Presence of a hematologic malignancy for which an alloHCT is indicated with a reduced toxicity or reduced intensity conditioning regimen
• Patients with polynuclear neutrophils > 0.5 G/L
• Patients having received wide spectrum antibiotics within the last 90 days prior to inclusion
• Karnofsky index = 70%
• Availability of a sibling donor, an unrelated stem-cell donor or a familial haploidentical donor
• Written informed consent

Ausschlusskriterien
• Patients planned to receive a non-myeloablative conditioning regimen (2 Gray total body irradiation (TBI) +/- purine analog, fludarabine + cyclophosphamide or equivalent)
• Patients planned to receive a conventional myeloablative conditioning regimen (e.g. high dose cyclophosphamide and high dose TBI (?10Gy); high dose busulfan (12.8 mg/kg IV) + high dose cyclophosphamide)
• Patients receiving a manipulated graft (in-vitro T-cell depletion)
• Patients planned to receive a conditioning regimen with alemtuzumab
• Patients planned to receive alloHCT with cord blood cells
• Patients planned to receive alloHCT from unrelated donor with >= 3/10 HLA-mismatches
• Patients receiving a large spectrum antibiotic at time of randomization
• Patients planned to receive vedolizumab or abatacept for GvHD prophylaxis
• Creatinine clearance <30 mL/min
• Bilirubin or amino-transferases abnormalities contra-indicating alloHCT
• Cardiac ejection fraction less than 40%
• Pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO)
• Pregnancy
• Confirmed or suspected intestinal ischemia
• Confirmed or suspected toxic megacolon or gastrointestinal perforation
• Any history of gastro-intestinal surgery in the past 3 months
• Any history of chronic digestive disease (Crohn's disease, ulcerative colitis, inflammatory bowel disease or other relevant digestive condition according to physician's judgement)
• Known allergy or intolerance to trehalose or maltodextrin
• Patients with EBV-IgG negative serology
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
• Vulnerable patients such as: persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention.

Studienteilnehmende Mindestalter
50 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Diverse

Medizinischer Befund
allogeneic hematopoietic cell transplantation

Institute
Klinik für Hämatologie und Stammzelltransplantation, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Amelie Boquoi

+49 (0)201 723-82530
amelie.boquoi@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Janssen Research & Development, LLC

Einschlusskriterien
* Have a diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria
* Be newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT) due to: ineligible due to advanced age OR; ineligible due to the presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT OR; deferral of high-dose chemotherapy with ASCT as initial treatment
* Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
* A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
* A participant must agree not to plan to father a child while enrolled in this study or within 100 days after the last dose of study treatment

Ausschlusskriterien
* Received any prior therapy for multiple myeloma or smoldering myeloma other than a short course of corticosteroids (not to exceed total of 160 milligrams [mg] dexamethasone or equivalent). * In addition, received a cumulative dose of systemic corticosteroids equivalent to greater than or equals to (>=) 20 mg of dexamethasone within 14 days before randomization
* Had plasmapheresis within 28 days of randomization
* Had a stroke, transient ischemic attack, or seizure within 6 months prior to randomization
* Known allergies, hypersensitivity, or intolerance to teclistamab or talquetamab excipients
* Known contraindications to the use of daratumumab or lenalidomide per local prescribing information
* Myeloma Frailty Index of >=2 with the exception of participants who have a score of 2 based on age alone

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
MM - Multiples Myelom

Medizinischer Befund
Multiple Myeloma

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
Diverse

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)

Dr. med. Stefan Alig

+49 (0)201 723-82530
stefan.alig@uk-essen.de

Hufelandstr.
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

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

Universitätsklinik Göttingen

Einschlusskriterien
Study Population
Patients with initial diagnosis of DLBCL qualified for a treatment with R-CHOP/ R-CHOP-like regime

1. Histological diagnosis of DLBCL&LBCL
2. Planned treatment with guideline-based first-line therapy
3. Patient's consent
4. All genders, Patient age = 18 years
5. Ability to consent

Ausschlusskriterien
1. Treatment with R-CHOP/-like regimens already started
2. Relationship of dependence/ direct employment with the investigator
3. Active HIV-infection
4. Presence history of other active cancers (with the exception of basal cell carcinoma of the skin)

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
85 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
DLBCL - Diffuses großzelliges B-Zell-Lymphom, NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
DLBCL - Diffuse Large B Cell Lymphoma

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. 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 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. 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. Bastian von Tresckow

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

Hufelandstraße 55
45147 Essen

Sponsor

Astra Zeneca AB, Schweden

Einschlusskriterien
o Aged 18 to 80 years old
o Histologically confirmed relapsed refractory FL (Module 1) and DLBCL (Module 2) after at least 2 prior lines of therapy
o ECOG performance status 0 to 2
o Locally confirmed CD-19 expression in lymphoma cells after progression from last CD 19 directed therapy
o FDG-avid disease with at least one bi-dimensionally measurable nodal lesion (defined as > 1.5 cm in its longest dimension), or extranodal lesion (defined as > 1.0 cm in its longest dimension)
o Adequate hematological function: ANC = 1000/mm3, platelets
? 75,000/mm3, hemoglobin = 9 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening
o Adequate liver function: total bilirubin <1.5x ULN, AST/ALT = 3xULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)
o Adequate renal function: creatinine clearance (CrCl) of = 45 mL/min
The above is a summary, other inclusion criteria details may apply.

Ausschlusskriterien
o Diagnosis of CLL, Burkitt lymphoma, or Richter's transformation
o Active CNS involvement by B-NHL
o Leukemic presentation of B-NHL
o 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
o Prior therapy with T-cell engager (TCE) within 8 weeks, CAR T- cell therapy or autologous Hematopoietic Stem Cell Transplantation (HSCT) within 12 weeks, or prior allogeneic HSCT within 24 weeks of first dose of AZD0486
o Requires chronic immunosuppressive therapy
o Unresolved non hematological AEs = Grade 2 from prior therapies; history of = Grade 3 CRS or neurotoxicity from prior CAR-T or TCE therapy
o History of major cardiac abnormalities.
o If female, participant must not be pregnant or breastfeeding.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
80 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
DLBCL - Diffuses großzelliges B-Zell-Lymphom, NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
B-cell Non-Hodgkin Lymphoma\nFollicular Lymphoma (FL)\nDiffuse Large B-Cell Lymphoma (DLBCL)

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

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. Thomas Schroeder

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

Hufelandstr. 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

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

Janssen Research & Development, LLC

Einschlusskriterien
• Be greater than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
• Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
• Participants with ET and MF with risk characteristics as described in the protocol
• Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (<=) 2

Ausschlusskriterien
• Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
• Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (>=) 3 years after treatment ended are allowed to enter the study
• Prior solid organ Transplantation
• Either of the following regarding hematopoietic stem cell transplantation:
1. Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or
2. Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
• History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment

Studienteilnehmende Mindestalter
18 Jahr(e)

Indikation
MPN - Myeloproliferative Neoplasie

Medizinischer Befund
CALR-mutated Myeloproliferative Neoplasms