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

ConditionCLL/SLL

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorStichting Hemato-Oncologie voor Volwassenen Nederland

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Parallel

Treatments tested in this trial

Epcoritamab
Drug
Number of cycles of epcoritamab is either 6 (cycle 1-6) or 12 (cycle 1-12). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.
Venetoclax
Drug
All patients will receive venetoclax cycle 1-26 (a 5 week ramp-up of venetoclax will precede the first cycle). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

Treatment groups

112 Participants

are divided into 2 treatment groups

Group A: Arm AExperimental treatment 2 interventions

Group B: Arm BExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

• Recommended phase II dose (RP2D) for the combination of venetoclax and epcoritamab based on dose limiting toxicity (DLT)

endpoint for phase I and both arms

Time frame

6-12 months

• Undetectable minimal residual disease <10-4 (uMRD) in BM in absence of progression according to IWCLL criteria at 12 weeks after cycle 26

endpoint for phase II and both arms

Time frame

29 months

Secondary outcomes

• Minimal residual disease (MRD) status in PB at cycle 4, 6, 9, 12, 15, 18, 21, 24 and 12 weeks after cycle 26; following treatment: every 3 months for the first year, then every 6 months until relapse or until 6 years after registration

both arms

Time frame

6 years

• Progression free survival (PFS), defined as time from registration to the first occurrence of disease progression or death from any cause, whichever occurs first.

both arms

Time frame

6 years

Overall survival (OS), defined as the time from registration to death from any cause.

both arms

Time frame

6 years

Best overall response rate (ORR) defined as the proportion of patients with a complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) according to IWCLL 2018 criteria.

both arms

Time frame

6 years