NCT03737981

Testing the Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemia

A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (>/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 465 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial compares adding a new anti-cancer drug (venetoclax) to the usual treatment (ibrutinib plus obinutuzumab) in older patients with chronic lymphocytic leukemia who have not received previous treatment. The addition of venetoclax to the usual treatment might prevent chronic lymphocytic leukemia from returning. This trial also will investigate whether patients who receive ibrutinib plus obinutuzumab plus venetoclax and have no detectable chronic lymphocytic leukemia after 1 year of treatment, can stop taking ibrutinib. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ibrutinib and obinutuzumab with venetoclax may work better at treating chronic lymphocytic leukemia compared to ibrutinib and obinutuzumab.

Detailed description

PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) between control treatment and experimental treatment strategies: ibrutinib/obinutuzumab (IO) with ibrutinib maintenance (IM) versus ibrutinib/venetoclax/obinutuzumab (IVO) regardless of IM or observation. SECONDARY OBJECTIVES: I. To compare bone marrow (BM) minimal residual disease (MRD)- complete response (CR) rates, MRD- rates, and depth of response at cycle 15 day 1 between patients treated with IO versus IVO. II. To compare overall survival (OS) between the control and experimental treatment strategies: IO with IM versus IVO regardless of IM or observation. III. To compare the 5-year PFS and overall survival (OS) for the control and experimental treatment strategies: IO with IM versus IVO regardless of IM or observation. IV. To describe the toxicity profile for each of the treatment strategies and by each treatment course. CORRELATIVES SCIENCE OBJECTIVES: I. To compare MRD status between blood and bone marrow at the end of induction treatment/cycle 15 day 1 to determine whether blood MRD can be used as a surrogate to bone marrow MRD with these treatment regimens. II. To compare peripheral blood MRD status by standard central flow cytometry to next generation sequencing (NGS) using ClonoSeq technique to determine the agreement in MRD negativity of the two techniques. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Treatment repeats every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 15, patients receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Beginning cycle 3, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. All patients will then receive a 15th cycle of ibrutinib. Beginning cycle 16, patients who do not achieve a BM MRD negative CR, receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a BM MRD negative CR undergo observation every 3 cycles for 6 years, then every 6 cycles thereafter. After completion of study treatment, patients are followed every 6 months until 10 years from registration.

Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	Ibrutinib	Given PO
BIOLOGICAL	Obinutuzumab	Given IV
OTHER	Observation Activity	Undergo observation
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2019-01-31
• Primary completion: 2025-01-17
• Completion: 2026-12-29
• First posted: 2018-11-13
• Last updated: 2026-04-13
• Results posted: 2026-02-02

Locations

860 sites across 1 country: United States

Regulatory

• FDA-regulated drug study