What is this study of acalabrutinib, obinutuzumab, and venetoclax trying to find out about high-risk chronic lymphocytic leukemia?

This study is evaluating whether the triple drug combination of acalabrutinib, obinutuzumab, and venetoclax can better delay disease progression compared to obinutuzumab and venetoclax alone in patients with high-risk chronic lymphocytic leukemia. The German CLL Study Group is leading this research to address treatment challenges in this aggressive form of leukemia. Participants receive fixed-duration, chemotherapy-free treatment options to assess improved outcomes.

Who may be eligible for this chronic lymphocytic leukemia clinical trial?

Adults aged 18 to 120 years with high-risk CLL defined by specific genetic factors such as 17p-deletion or TP53 mutation may be eligible. Participants must not have had prior CLL-specific treatments except limited corticosteroids and need adequate organ function. Both males and females can join. Please review eligibility criteria for more details.

Is there any cost to participate in this chronic lymphocytic leukemia clinical trial?

Study-related care, including the study drugs and all trial visits, is provided at no cost. However, personal travel and related expenses may vary and are not guaranteed to be covered. Participants should plan accordingly for any out-of-pocket costs during their involvement.

Actively Recruiting

Phase 3

Age: 18Years - 120Years

All Genders

ID05197192

A Phase 3 Trial Comparing Acalabrutinib, Obinutuzumab, and Venetoclax Versus Obinutuzumab and Venetoclax in Previously Untreated High-Risk Chronic Lymphocytic Leukemia

Led by German CLL Study Group · Updated on 2025-08-17

202

Participants Needed

Research Sites

N/A

Total Duration

AI-Summary

What this Trial Is About

Researchers are evaluating treatments for patients with high-risk chronic lymphocytic leukemia CLL, a type of blood cancer that is aggressive and currently incurable. This phase 3, open-label, multicenter, randomized study aims to compare the effectiveness of a triple drug combination acalabrutinib, obinutuzumab, and venetoclax against a double combination obinutuzumab and venetoclax in prolonging progression-free survival PFS for patients with specific high-risk genetic features such as 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV gene status. The study addresses a crucial medical need for better treatments in this difficult-to-treat group. Participants will be randomly assigned to one of two treatment groups. One group receives the triple combination of acalabrutinib, obinutuzumab, and venetoclax, while the other group receives obinutuzumab plus venetoclax. Obinutuzumab is given as intravenous infusions on specific days across six cycles. Venetoclax is taken orally with a carefully planned dose escalation and maintenance over 12 cycles. Acalabrutinib is administered orally twice daily during cycles 15 to 24. The study explores whether adding acalabrutinib improves outcomes by using these fixed-duration, chemotherapy-free regimens. Throughout the study, participants will undergo regular assessments to monitor response and safety, including checks for minimal residual disease MRD and overall survival. These evaluations occur up to 50 months after the first patient is enrolled. Researchers will also track progression-free survival, complete and overall response rates, event-free survival, duration of response, and time to next treatment. Safety monitoring and laboratory tests will be performed as part of study visits. The total study participation is expected to last several years to capture long-term outcomes for this high-risk patient population.

CONDITIONS

Brief Title

A Phase-3-trial of Acalabrutinib, Obinutuzumab & Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk CLL

Who Can Participate

Age: 18Years - 120Years

All Genders

Eligibility Criteria

You may qualify if you...

Documented diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) requiring treatment according to iwCLL criteria
Age 18 years or older
Presence of at least one high-risk factor: 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV gene status
Life expectancy of at least six months
Platelet count greater than 30 x 10^9/l indicating adequate bone marrow function
Creatinine clearance of 30 ml/min or higher
Adequate liver function with total bilirubin no more than 2 times and AST/ALT no more than 2.5 times the institutional upper limit, unless related to CLL or Gilbert's Syndrome
Negative testing for hepatitis B and hepatitis C as specified
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

You will not qualify if you...

Previous CLL-specific treatments, except corticosteroids up to 20 mg prednisolone equivalent within 10 days before study start
Absence of high-risk disease (no 17p-deletion, TP53 mutation, or complex karyotype)
Severe organ or system impairment (score of 4 by CIRS), including advanced cardiac disease (NYHA class 3 or 4) limiting treatment ability
Any life-threatening illness or condition that could affect safety or drug absorption, such as inability to swallow or gastrointestinal issues
Transformation of CLL to Richter syndrome
Other malignancies currently needing systemic therapy
Active or uncontrolled infections including HIV or PML
Use of anticoagulant therapy with warfarin or phenoprocoumon
Pregnant or nursing women

Research Team

Barbara Eichhorst, MD, Prof.

Anna Fink, MD

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