Studien

Institut
Med.Klinik Hämatologie

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Alexander Carpinteiro

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

Hufelandstr 55
45147 Essen

Einschlusskriterien
histologisch gesicherte Amyloidose oder positive Skelettszintigrafie

Ausschlusskriterien
lokale Amyloidose des ZNS

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
AL-Amyloidose

Medizinischer Befund
Amyloidose

Institut
Med.Klinik Hämatologie

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
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
AML - Akute myeloische Leukämie

Medizinischer Befund
AML

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
DLBCL - Diffuses großzelliges B-Zell-Lymphom

Medizinischer Befund
Diffuse Large B-cell lymphoma (DLBCL)

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ITP - idiopathische thrombozytopenische Purpura

Medizinischer Befund
Primary Immune Thrombocytopenia (ITP)

MedDRA Term
Idiopathic thrombocytopenic purpura

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
CLL - Chronische lymphatische Leukämie

Medizinischer Befund
CLL\nChronic Lymphocytic Leukemia

Institute
Med.Klinik Hämatologie, Neurologie

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
60 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
Relapsing multiple sclerosis, Myasthenia gravis, Multiple sclerosis, Progressive multiple sclerosis

Institute
Med.Klinik Hämatologie, 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

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
Primary Central Nervous System Lymphoma (PCNSL)

Institute
Med.Klinik Hämatologie, 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

Bristol-Myers Squibb

Einschlusskriterien
• Participants = 18 years of age with R/R NHL (including DLBCL [ie, DLBCL not otherwise specified (NOS) and diffuse large B-Cell lymphoma/high-grade B-Cell lymphoma with MYC and BCL2 rearrangements], and FL):
o For R/R DLBCL (de novo) and FL 3b: following at least 2 prior lines of therapy (eg, first-line combination chemotherapy regimen containing rituximab, anthracycline, an alkylating agent, and steroids and at least one additional treatment).
o For R/R DLBCL (transformed lymphoma): following at least 2 prior lines of therapy which must have been administered after transformation.
o For R/R FL (except for FL 3b): following at least 2 prior lines of therapy and meeting treatment criteria at the time of enrollment based on investigator´s assessment.
• Participant must have measurable disease (defined by at least one FDG-avid lesion for FDG-avid disease and one bi-dimensionally measurable disease on cross sectional imaging by computed tomography or magnetic resonance imaging with at least one lesion > 1.5 cm in the transverse diameter).
• Participants must accept and follow pregnancy prevention plan.

Ausschlusskriterien
• Participants must not have an Eastern Cooperative Oncology Group (ECOG) performance status ? 2.
• Participants with an inability to comply with listed restrictions, precautions and prohibited treatments.
• Participants must not have prior CAR-T, or radiotherapy ? 4 weeks, systemic anticancer treatment ? 5 half-lives or 4 weeks, allogeneic SCT ? 6 months (only applicable to BMS-986458 single agent or rituximab combination cohorts), or autologous SCT ? 3 months prior to study intervention initiation.
• In BMS-986458 + T-cell engager combination cohorts: Participants must not have prior alloSCT or solid organ transplantation, history of confirmed progressive multifocal leukoencephalopathy (PML); known or suspected history of hemophagocytic lymphohistiocytosis (HLH); known or suspected chronic active Epstein-Barr (EBV) infection.
• Participants must not have any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
• Participants must not have known or suspected central nervous system involvement.

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
Relapsed\/Refractory Non-Hodgkin Lymphoma (NHL)

Institute
Med.Klinik Hämatologie, 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
Med.Klinik Hämatologie, 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 Münster

+49 (0)251 83-55555
info@ukmuenster.de

Albert-Schweitzer-Straße 33
48149 Münster

Studienteilnehmende Mindestalter
Jahr(e)

Indikation
DLBCL - Diffuses großzelliges B-Zell-Lymphom

Medizinischer Befund
Relapsed\/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Institute
Med.Klinik Hämatologie, 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
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
Med.Klinik Hämatologie, 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
Jahr(e)

Indikation
CLL - Chronische lymphatische Leukämie

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

Institut
Med.Klinik Hämatologie

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

Institut
Med.Klinik Hämatologie

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Ferras Alashkar

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

Hufelandstraße 55
45147 Essen

Sponsor

Sanofi US

Einschlusskriterien
• Participants who have been diagnosed with SCD.
• Participants who have had between ?2 and ?10 episodes of documented clinical VOC within 12 months of the screening events.
• Participants who are either not on hydroxyurea and/or L-glutamine at the Screening Visit and does not plan to receive them during the course of the study or has received HU and/or L-glutamine for a minimum of 6 months. Participants on hydroxyurea and/or L-glutamine must have been on a stable weight-based dose level (mg/kg) for at least 3 months prior to the Screening Visit, with the intent to continue at the same weight-based dose level for the duration of the study, except for safety reasons.
• Participants with Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• For participants ?10 to <18 years of age: the parent(s)/legal guardian(s) must provide written informed consent prior to any study-related procedures being performed.

Ausschlusskriterien
• Participants are excluded from the study if any of the following criteria apply: Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.
• Clinically relevant cardiac abnormality, in the opinion of the Investigator or electrocardiogram (ECG) findings.
• Participants with history of stroke, or history of abnormal transcranial doppler.
• Participants with uncontrolled or active HBV infection and/or HCV infection including those receiving antiviral therapy at the time of screening.
• HIV infection.
• A history of active or latent tuberculosis (TB)
• Positive COVID-19 molecular test.
• Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days and/or voxelotor (OXBRYTA®) within 30 days prior to the Screening visit.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Studienteilnehmende Mindestalter
65 Jahr(e)

Studienteilnehmende Höchstalter
65 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Diverse

Medizinischer Befund
sickle-cell disease (SCD)

Institute
Med.Klinik Hämatologie, 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
60 Jahr(e)

Studienteilnehmende Höchstalter
60 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
HD - Hodgkin Lymphom

Medizinischer Befund
Hodgkin-Lymphom Lymphogranulomatose

Institute
Med Klinik Kardiologie, Med.Klinik Hämatologie, Neurologie

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Alexander Carpinteiro

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

Hufelandstr 55
45147 Essen

Sponsor

Universitätsklinik Essen (AöR)

+49 (0)201 723-0
info@uk-essen.de

Hufelandstraße 55
45147 Essen

Geschlecht
Divers, Männlich, Weiblich

Indikation
AL-Amyloidose

Medizinischer Befund
Amyloidose

Institute
Med.Klinik Hämatologie, Strahlentherapie, 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)
o Untreated (radiation-, chemo- or immunotherapy) nodal follicular lymphoma (including involvement of Waldeyer´s ring)
o Age: ?18 years
o ECOG: 0-2
o Stage: clinical stage I or II (Ann Arbor classification) based on FDG-PET Staging
o Risk profile: Largest diameter of the lymphoma ? 7 cm (sectional images)
o Written informed consent and willingness to cooperate during the course of the trial
o Adequate bone marrow capacity: ANC ? 1.5 x 103/ml, thrombocytes ? 100000 x 10 3/ml, hemoglobin ? 10 g/dL
o Capability to understand the intention and the consequences of the clinical trial
o 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
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 I, Non-Hodgkin's lymphoma stage II

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Indikation
Solide Tumoren

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

Institute
Med.Klinik Hämatologie, 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

Geschlecht
Divers, Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom, Diverse Tumorerkrankungen

Medizinischer Befund
Lymphoma

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Indikation
ALL - Akute lymphatische Leukämie

Institut
Med.Klinik Hämatologie

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Thomas Schroeder

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

Hufelandstr. 55
45147 Essen

Sponsor

Incyte Corporation, DE, USA

Geschlecht
Divers, Männlich, Weiblich

Indikation
Diverse, GVHD (Graft-Versus-Host Disease)

Medizinischer Befund
Chronic Graft Vs. Host Disease (cGVHD)

Institut
Med.Klinik Hämatologie

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
Med.Klinik Hämatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Amelie Boquoi

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

Hufelandstr. 55
45147 Essen

Indikation
MM - Multiples Myelom

Medizinischer Befund
Multiples Myelom

Institut
Med.Klinik Hämatologie

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Alexander Röth

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

Hufelandstraße 55
45147 Essen

Sponsor

Sanofi US

Einschlusskriterien
• Male or female participants aged 18 years and older with primary ITP
• Participant received at least a first line therapy and had a history of response while on treatment
• Participant has loss of response, relapse or steroid dependency

Ausschlusskriterien
• Participants with Secondary ITP
• Participants with Evans syndrome or history of myelodysplastic syndrome
• Participants with history of lymphoma, leukemia, or any malignancy within the past 5 years except for non-melanoma skin malignancy.
• Participants with history of solid organ transplant
• Participants with history of coagulation or bleeding disorders other than ITP
• Participant received advanced therapy for ITP or was splenectomized
• Pregnancy or nursing The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ITP - idiopathische thrombozytopenische Purpura

Medizinischer Befund
Immune Thrombocytopenia (ITP)

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
CLL - Chronische lymphatische Leukämie

Medizinischer Befund
Rezidivierende chronisch lymphatische Leukämie

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Diverse

Medizinischer Befund
allogeneic hematopoietic cell transplantation

Institute
Klinik für Kinderheilkunde III, Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Männlich

Indikation
Diverse

Medizinischer Befund
Steroid refractory Acute Graft versus host Disease

MedDRA Term
Acute graft versus host disease

Institute
Med.Klinik Hämatologie, 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/?L
- Platelets ?75.000 cells/?L
- 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
Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
MCL - Mantelzelllymphom

Medizinischer Befund
Mantle Cell Lymphoma

MedDRA Term
Mantle cell lymphoma NOS

Institute
Med.Klinik Hämatologie, 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
85 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
Med.Klinik Hämatologie, 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
Med.Klinik Hämatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Bastian von Tresckow

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

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinikum Köln

Einschlusskriterien
- age 18-60
- advanced stage classical Hodgkin Lymphoma
- no previous treatment for cHL

Ausschlusskriterien
- Nodular lymphocyte-predominant Hodgkin lymphoma or composite lymphoma
- Chemotherapy or radiotherapy in medical history
- Prior or concurrent disease that prevents treatment according to protocol

Studienteilnehmende Mindestalter
60 Jahr(e)

Studienteilnehmende Höchstalter
60 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
HD - Hodgkin Lymphom

Medizinischer Befund
Hodgkin Lymphoma

Institute
Med.Klinik Hämatologie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Andreas Hüttmann

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

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsmedizin Berlin

Augustenburger Platz 1
13353 Berlin

Einschlusskriterien
Alle Patienten mit PTLD

Ausschlusskriterien
keine

Studienteilnehmende Mindestalter
99 Jahr(e)

Studienteilnehmende Höchstalter
99 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom

Medizinischer Befund
Posttransplantations-Lymphoproliferative Erkrankungen (PTLD)

Institute
Med.Klinik Hämatologie, 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
120 Jahr(e)

Studienteilnehmende Höchstalter
120 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
ZNS - Lymphom mit Befall des zentralen Nervensystems

Medizinischer Befund
CNS Lymphoma

Institute
Med.Klinik Hämatologie, 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

Regeneron Pharmaceuticals, Inc, USA

Einschlusskriterien
1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator, as described in the protocol.
2. Must have refractory disease or relapsed after at least 1 prior line (with a duration of at least 2 cycles) of systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-Cluster of Differentiation 20 (CD20) monoclonal antibody and participant should meet indication for treatment, as described in the protocol.
3. Have measurable disease on cross sectional imaging documented by diagnostic Computed Tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Adequate hematologic and organ function, as described in the protocol.
6. All study participants must:
1. Have an understanding that lenalidomide could have a potential teratogenic risk.
2. Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide.
3. Agree not to share study medication with another person.
4. Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide.
Note: Other protocol-defined Inclusion criteria apply

Ausschlusskriterien
1. Primary Central Nervous System (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS NHL, as described in the protocol.
2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL.
3. History of or current relevant CNS pathology, as described in the protocol.
4. A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.
5. Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol.
6. Allergy/hypersensitivity to study drugs or excipients. as described in the protocol.
7. Active infection as defined in the protocol.
Note: Other protocol-defined Exclusion criteria apply

Studienteilnehmende Mindestalter
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
NHL - Non-Hodgkin-Lymphom, NHL ind. - indolentes Non-Hodgkin Lymphom

Medizinischer Befund
Relapsed\/Refractory Follicular Lymphoma\nRelapsed\/Refractory Marginal Zone Lymphoma (MZL)

MedDRA Term
Follicular lymphoma, Extranodal marginal zone B-cell lymphomas (low grade B-cell), Splenic marginal zone lymphomas, Nodal marginal zone B-cell lymphomas, Follicle centre lymphomas follicular grade I II III

Institute
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
PNH - Paroxysmale nächtliche Hämoglobinurie

Medizinischer Befund
Paroxysmal Nocturnal Hemoglobinuria

Institute
Med.Klinik Hämatologie, 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
80 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
Med.Klinik Hämatologie, Westdeutsches Tumorzentrum, Westdeutsches Tumorzentrum Münster

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Thomas Schroeder

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

Hufelandstr. 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
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
Med.Klinik Hämatologie, 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

Indikation
Diverse

Medizinischer Befund
acute myeloid leukemia OR high-risk myelodysplastic Neoplasia with IDH1 mutation

Institute
Med.Klinik Hämatologie, 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
70 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
Med.Klinik Hämatologie, 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
Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
MPN - Myeloproliferative Neoplasie

Medizinischer Befund
CALR-mutated Myeloproliferative Neoplasms