Zanubrutinib With Obinutuzumab in Untreated Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Sponsor
PETHEMA Foundation
Study ID
NCT06544785
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Zanubrutinib Oral Product — DRUG
    Zanubrutinib drug product is supplied as 80 mg strengths in capsules for oral administration. In both arms A and B, zanubrutinib 320 mg will be taken qDay with or without food. Patients will take zanubrutinib with water at approximately the same time every day.
  • Obinutuzumab — DRUG
    Each dose of obinutuzumab is 1000 mg administered intravenously, per institutional standards, with the exception of the first infusion in Cycle 2 (arm A) or Cycle 13 (arm B). It is recommended that the initial 1000 mg dose be administered over Day 1 (100 mg) and Day 2 (900 mg). For subjects who tolerate the initial 100 mg dose well and required no dose interruption or modification of the infusion rate, the treating physician may opt to administer the remaining 900 mg on Day 1. Arm A: patients will receive obinutuzumab on days 1 (100 mg), 2 (or day 1 continued, 900 mg), 8 and 15 (1000 mg) of the cycle 2 of zanubrutinib treatment, and on the day 1 of cycles 3-7 (1000 mg). Arm B: patients will receive obinutuzumab on days 1 (100 mg), 2 ( (or day 1 continued, 900 mg), 8 and 15 (1000 mg) of the cycle 13 of zanubrutinib treatment, and on the day 1 of cycles 14-18 (1000 mg).

Study Details

The goal of this phase II randomized open label study is to compare the rate of complete remission (CR) with undetectable minimal residual disease (uMRD) obtained with zanubrutinib in combination with obinutuzumab with two different schedules of administration of obinutuzumab (starting obinutuzumab at cycle 2 or 12 months) in patients with previously untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). There is scarce information about which is the most appropriate schedule of combining the BTKi and the anti-CD20 monoclonal antibody, and whether treatment can be safely stopped in those patients attaining deep responses (CR with uMRD) remains to be determined. Response will be assessed after 20 cycles of treatment for the primary objective of the study. Patients attaining uMRD will stop treatment with zanubrutinib, whereas the rest of patients will continue on treatment with zanubrutinib until progression, unacceptable toxicity, or trial completion, whichever comes first.

Key Dates

First listed
Aug 9, 2024
Start date
Sep 2, 2024
Status verified
Jun 2026
Primary completion
May 31, 2032
Completion
May 31, 2032

Study Design

Enrollment
106 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm Zanubrutinib+early Obinutuzumab
    Patients will be treated with the combination of zanubrutinib 320 mg P.O qDay and obinutuzumab, starting obinutuzumab at cycle 2 to reduce infusion-related reactions. Intravenous obinutuzumab will be given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 2 and on day 1 (1000 mg) of cycles 3-7. Response will be assessed after 20 cycles of treatment for the primary objective of the study. Patients that in the evaluation of cycle 20 who achieve uMRD will stop treatment with zanubrutinib, whereas the rest of patients will continue on treatment with zanubrutinib until progression, unacceptable toxicity or trial completion, whichever comes first. Patients who achieve an uMRD in bone marrow beyond C20, will also be allowed to stop the treatment, whereas the rest of patients will continue on treatment with zanubrutinib until progression, unacceptable toxicity, or trial completion, whichever comes first.
  • Experimental: Arm Zanubutinib+late Obinutuzumab
    Patients will start treatment with zanubrutinib 320 mg P.O qDay in monotherapy. After 12 cycles of zanubrutinib patients will be treated with the combination of zanubrutinib and obitnutuzumab. Intravenous obinutuzumab will be given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 13 and on day 1 (1000 mg) of cycles 14-18. Response will be assessed after 20 cycles of treatment for the primary objective of the study. Patients that in the evaluation of cycle 20 who achieve uMRD will stop treatment with zanubrutinib, whereas the rest of patients will continue on treatment with zanubrutinib until progression, unacceptable toxicity or trial completion, whichever comes first. Patients who achieve an uMRD in bone marrow beyond C20, will also be allowed to stop the treatment, whereas the rest of patients will continue on treatment with zanubrutinib until progression, unacceptable toxicity, or trial completion, whichever comes first.

Primary Outcome Measure

Rate of Complete Remission (CR) with undetectable Measurable Residual Disease (uMRD). [ Time Frame: 7.5 Years ]

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