Venetoclax Treatment (26 Cycles) With 6 Cycles or 12 Cycles of Epcoritamab in Patients With Relapsed or Refractory CLL or SLL

Recruiting now · Phase 1/Phase 2

Conditions studied: CLL/SLL

In brief

In this study, efficacy and safety of 2 regimens that combine the CD3-CD20 T cell engager epcoritamab with venetoclax will be tested in relapsed/refractory CLL and SLL patients. The trial starts with phase I part to establish the recommended dose level (RDL) of epcoritamab in the combination with venetoclax for the phase II trial.

Key facts

Study ID: NCT05791409
Run by: Stichting Hemato-Oncologie voor Volwassenen Nederland
People needed: 112
Starts: 2024-04-10
Expected to finish: 2032-11-01
Last updated by the study team: 2024-04-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Documented relapsed or refractory CLL or SLL (SLL in phase II part only) following at least one systemic 1st-line treatment
Requiring treatment according to IWCLL criteria (appendix A);
Age at least 18 years;
ECOG/WHO performance status 0-2;
In case of prior venetoclax treatment, enrollment can only occur at least 24 months after end of treatment and patients must not have progressed during venetoclax treatment;
Adequate BM function defined as:
Hemoglobin >5.6 mmol/l or Hb > 9 g/dL, unless low Hb is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
Absolute neutrophil count (ANC) >1.0 x 109/L (1,000/μL), unless low ANC is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
Platelet count >30 x 109/L (30,000/μL), unless low platelets is directly attributable to CLL infiltration in the BM;
Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/min (Cockcroft-Gault appendix F);
Adequate liver function as indicated:
Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 3.0 x upper limit of normal (ULN);
Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or controlled autoimmune hemolytic anemia);
Prothrombin time (PT)/International normal ratio (INR) <1.5x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN; unless receiving anticoagulation;
Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded; Please note: For patients positive for anti-HBc, HBV-DNA PCR has to be repeated every month until 12 months after last dose of study treatment.
Patient is able and willing to adhere to the study visit schedule and other protocol requirements;
Patient is capable of giving informed consent;
Written informed consent.

You may not qualify if…

Active CLL/SLL directed therapy within the last 14 days;
Prior treatment with a CD3 × CD20 bispecific antibody or CAR T-cell therapy
Transformation of CLL (Richter's transformation);
Prior allogeneic stem cell transplantation and/or solid organ transplantation;
Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML);
Malignancies other than CLL currently requiring systemic therapy or not treated in curative intention or showing signs of progression after curative treatment;
Known allergy to xanthine oxidase inhibitors and/or rasburicase;
History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components);
Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease);
Active fungal, bacterial, and/or viral infection CTCAEgrade > 1; Please note: active controlled as well as chronic/recurrent infections are at risk of reactivation/infection during treatment;
Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, auto-immune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.);
Patient known to be HIV-positive;
Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor/inducer (see appendix J) or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists;
CTCAE grade III-IV cardiovascular disease including but not limited to:
Unstable or uncontrolled disease/condition related to or affecting cardiac function, eg, unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association (see appendix E), uncontrolled clinically significant cardiac arrhythmia (CTCAE grade II or higher), or clinically significant electrocardiogram (ECG) abnormalities.
Myocardial infarction, intracranial bleed, or stroke within the past 6 months.
Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >480 msec. NOTE: this criterion does not apply to subjects with a left bundle branch block.
Stroke or intracranial hemorrhage within 6 months prior to registration.
Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);
Severe neurological or psychiatric disease (CTCAE grade III-IV, see appendix D);
Neuropathy > CTCAE grade II
Patient who has difficulty with or are unable to swallow oral medication, or have significant gastrointestinal disease that would limit absorption of oral medication;
Vaccination with live vaccines within 28 days prior to registration;
Use of any other experimental drug or therapy within 28 days of registration;
Major surgery within 28 days prior to registration;

Where it is running

DK-Copenhagen-RIGSHOSPITALET — Copenhagen, Denmark (enrolling)
BE-Roeselare-AZDELTA — Roeselare, Belgium
DK-Aalborg-ALBOGUH — Aalborg, Denmark
DK-Odense-OUH — Odense, Denmark
DE-Berlin-HELIOSBERLINBUCH — Berlin, Germany
DE-Köln-UKKOELN — Cologne, Germany
DE-Freiburg-UNIKLINIKFREIBURG — Freiburg im Breisgau, Germany
DE-Greifswald-UNIGREIFSWALD — Greifswald, Germany
DE-Munster-GEMEINSCHAFTSPRAXIS — Münster, Germany
DE-Stuttgart-RBK — Stuttgart, Germany
DE-Ulm-UNIKLINKULM — Ulm, Germany
NL-Den Bosch-JBZ — 's-Hertogenbosch, Netherlands
NL-Alkmaar-NWZ — Alkmaar, Netherlands
NL-Amersfoort-MEANDERMC — Amersfoort, Netherlands
NL-Amsterdam-AMC — Amsterdam, Netherlands
NL-Dordrecht-ASZ — Dordrecht, Netherlands
NL-Ede-ZGV — Ede, Netherlands
NL-Eindhoven-CATHARINA — Eindhoven, Netherlands
NL-Groningen-UMCG — Groningen, Netherlands
NL-Leeuwarden-MCL — Leeuwarden, Netherlands
NL-Den Haag-HAGA — The Hague, Netherlands
NL-Tilburg-ETZ — Tilburg, Netherlands
BE-Antwerpen-ZNASTUIVENBERG — Antwerp, Belgium
NL-Utrecht-UMCUTRECHT — Utrecht, Netherlands

Full record on ClinicalTrials.gov

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