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

Exclusion Criteria30

• 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;
• Pregnant women and nursing mothers;
• Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device, sexual abstinence or combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) during study treatment and for 12 months after last dose of epcoritamab and 30 days after last dose of venetoclax;
• Previous participation in the HOVON 139 CLL or HOVON 140 CLL trial and eligible for and willing to participate in the HOVON 159 CLL trial;
• Current participation in other clinical trial with medicinal products;
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.