Actively Recruiting
A Phase 1/2 Study of Acalabrutinib, Venetoclax, and Obinutuzumab in Patients With Relapsed/Refractory and Previously Untreated Mantle Cell Lymphoma
Led by Austin I Kim · Updated on 2026-01-21
72
Participants Needed
3
Research Sites
26 weeks
Total Duration
On this page
Sponsors
A
Austin I Kim
Lead Sponsor
R
Roche-Genentech
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of three drugs—acalabrutinib, venetoclax, and obinutuzumab—as a possible treatment for people with relapsed, refractory, or untreated mantle cell lymphoma (MCL). This open-label, phase 1/2 study is designed to assess the safety and effectiveness of this combination, with a focus on determining the appropriate dose and measuring treatment responses. The study is expected to enroll about 72 participants and will include different groups based on prior treatment history and genetic markers related to TP53 mutation status. The study consists of four parts, each targeting specific groups of participants with mantle cell lymphoma. Participants will receive the three drugs on different schedules within 28-day treatment cycles: acalabrutinib is given orally starting from cycle 1, venetoclax orally starting from cycle 3, and obinutuzumab via intravenous infusion starting from cycle 2. Treatment continues as long as there are no severe side effects and the disease does not worsen. Some participants will receive additional maintenance therapy. Follow-up will continue for up to five years to monitor long-term outcomes. Participants will undergo screening to confirm eligibility and will have regular evaluations throughout the study, including imaging scans, blood tests, and bone marrow samples. Researchers will monitor treatment response rates, minimal residual disease status, progression-free survival, overall survival, and safety measures such as adverse events and infusion reactions. The study includes detailed assessments over months and years to understand how participants respond to this treatment combination and to track any side effects or disease progression.
CONDITIONS
Brief Title
Avo In R/R And Previously Untreated MCL
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Histologically confirmed mantle cell lymphoma with pathologic review
- Relapsed or refractory after at least one prior therapy including anti-CD20 monoclonal antibody (Part A) or untreated requiring treatment (Parts B, C, D)
- Prior stem cell transplant or CAR T-cell therapy allowed for Part A
- Untreated participants in Part B must be transplant ineligible and/or have TP53 mutation
- Untreated participants in Part C must be transplant eligible and TP53 wild type
- Untreated participants in Part D must have TP53 mutation
- Archived tumor tissue and peripheral blood samples available for molecular marker testing
- Measurable disease by imaging or marrow involvement with cytopenias or symptomatic splenomegaly
- ECOG performance status 0 to 2
- Adequate organ and marrow function as specified
- Willingness to provide bone marrow and blood samples
- Women of child-bearing potential must use effective contraception during and after treatment; men must use contraception and avoid sperm donation during and after treatment
- Ability to understand and sign informed consent
You will not qualify if you...
- Progression or relapse after BTK or BCL2 inhibitor therapy
- Use of other investigational agents within 4 weeks
- Concurrent systemic immunosuppressants or high-dose corticosteroids
- Severe allergic reactions to study drugs or similar compounds
- History of other active malignancies except certain treated cancers
- Known brain or leptomeningeal metastases
- Recent major surgery or traumatic injury within 4 weeks
- Recent live vaccine administration
- Active HIV, hepatitis B or C infection
- Ongoing infection needing IV antibiotics
- Uncontrolled illness or psychiatric conditions limiting compliance
- Pregnant or lactating women
- Known bleeding disorders or recent gastrointestinal bleeding
- Recent stroke or intracranial hemorrhage
- Need for warfarin or vitamin K antagonists
- Significant cardiovascular disease or recent cardiac events
- Use of strong CYP3A or P-gp inhibitors/inducers without washout
- Unable to swallow oral medication or have gastrointestinal conditions affecting absorption
- Significant comorbidities posing undue risk
- History of progressive multifocal leukoencephalopathy (PML)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - Variable, until disease progression or unacceptable side effects
Participants receive the combination of acalabrutinib, venetoclax, and obinutuzumab according to the study schedule. Treatment cycles last 28 days each and continue as long as there are no serious side effects and the disease does not get worse.
Study drug administration and assessments occur during multiple treatment cycles, including oral medications and intravenous infusions as scheduled
Duration - Up to 5 years
Participants are followed for up to 5 years after treatment to monitor long-term outcomes and safety.
Trial Site Locations
Total: 3 locations
1
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Actively Recruiting
2
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Actively Recruiting
3
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
Research Team
A
Austin I Kim, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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