Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab

Part of paid clinical trials in New York, New York.

Sponsor
Weill Medical College of Cornell University
Study ID
NCT05650723
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Leukemia, Lymphocytic, Chronic, B-Cell

Eligibility Criteria

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

Interventions

  • Zanubrutinib Pill — DRUG
    320 mg once per day by mouth
  • Venetoclax Pill — DRUG
    400 mg once per day by mouth following the standard ramp-up schedule (20mg daily PO week 1, 50mg daily PO week 2, 100mg daily PO week 3, 200mg daily PO week 4, followed by 400mg PO daily week 5)
  • Obinutuzumab Injection — DRUG
    1000 mg IV given every 28 days

Study Details

Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. The investigators hypothesis is that it may be better to give anti-CD20 therapy (obinutuzumab) only to patients that still have detectable cancer in their blood (minimal residual disease \[MRD\]) after being treated with a combination of two oral medications, zanubrutinib (a BTKi ) and venetoclax (a BCL-2i), instead of giving a combination of three drugs to all patients from the start of treatment. This strategy, if effective, will prevent overtreatment with anti-CD20 antibodies; reduce side effects of treatment while potentially increasing MRD negativity rates; and will possibly make the anti-CD20 antibody therapy more effective given the low tumor burden present when utilized. This study will test this hypothesis by treating subjects with 3 cycles of a zanubrutinib monotherapy lead-in, in order to debulk and mitigate tumor lysis risk, followed by 13 cycles of zanubrutinib and venetoclax combination therapy. Subjects who are both peripheral blood and bone marrow MRD negative at the completion of the 13 cycles of combination therapy will stop treatment and enter an observation phase every 3 months. Subjects that are MRD positive will continue combination therapy with zanubrutinib and venetoclax for an additional 6 cycles but also receive 6 cycles of obinutuzumab in order to augment response and increase MRD negative rates for the overall treated cohort.

Key Dates

Start date
May 8, 2023
Status verified
Feb 2026
Primary completion
Mar 31, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
50 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Double Therapy (Zanubrutinib plus Venetoclax)
    All participants will receive an initial 3 cycles of zanubrutinib monotherapy. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination therapy. All participants will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Participants will continue on double combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all participants will be on treatment for at least 16 full cycles. Participants that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Participants that remain MRD positive at C16D1 will enter the triple therapy (zanubrutinib, venetoclax, and obinutuzumab) arm.
  • Experimental: Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab)
    Participants that meet definition of MRD positivity at C16D1 will enter the triple therapy arm (zanubrutinib, venetoclax, and obinutuzumab). These participants will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all participants will stop study treatment regardless of MRD status.

Primary Outcome Measure

Percentage of total patients that have achieved undetectable minimal residual disease (MRD) at cycle 16, as assessed via peripheral blood [ Time Frame: Cycle 16 (Month 16) ]

Locations (1)

FacilityCityStateZIPSite coordinators
Weill Cornell Medicine/NewYork-Presberteryian HospitalNew YorkNew York10021-

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By research site
Weill Cornell Medicine/NewYork-Presberteryian Hospital· New York, NY

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