Status and phase
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Treatments
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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:
Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/min (Cockcroft-Gault appendix F);
Adequate liver function as indicated:
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.
Exclusion criteria
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:
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.
Primary purpose
Allocation
Interventional model
Masking
112 participants in 2 patient groups
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Central trial contact
Mark-David Levin; Arnon Kater
Data sourced from clinicaltrials.gov
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