Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab

Launched by ASTRAZENECA · Jun 9, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have had their cancer come back after initial therapy. Specifically, it will look at how well a combination of two medicines, acalabrutinib and venetoclax, works when given for a set period of time. These patients must have already received and responded to a first round of treatment that included similar types of medicines, and they must have stayed in good health for at least two years after that treatment ended.

To join this study, participants need to be adults diagnosed with CLL or SLL and have responded to their first treatment with certain targeted drugs. They also need to have good organ function and be generally well enough to take part, based on a standard health assessment. Before starting the new treatment, doctors will check for specific genetic markers in the cancer cells to help guide therapy. Participants will be closely monitored for safety and how well the treatment controls the disease. This study is not yet recruiting, but it offers hope for patients looking for effective options after their initial treatment has stopped working.

Gender

ALL

Eligibility criteria

• Main Inclusion Criteria:
• • 1. Participant must be ≥ 18 years at the time of signing informed consent.
• • 2. Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)
• • 3. Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) with a minimum of 2 years since the end of the prior 1L treatment.
• 4. The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:
• • 1. IGHV (mutated vs. unmutated)
• • 2. del(17p) (present or absent)
• • 3. TP53 mutation (present or absent)
• • 5. ECOG performance status 0, 1 or 2
• • 6. Adequate organ and bone marrow (BM) function.
• Main Exclusion Criteria:
• • 1. Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
• • 2. Significant cardiovascular or cerebrovascular disease.
• • 3. Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
• • 4. Child-Pugh B/C liver cirrhosis.
• • 5. History of prior or current malignancy.
• • 6. HIV positive
• • 7. History of progressive multifocal leukoencephalopathy (PML).
• 8. Active hepatitis B or C infection:
• • 9. Corticosteroid use \> 20 mg within 1 week before the first dose of study intervention.
• • 10. History of hypersensitivity or anaphylaxis to study intervention(s).
• • 11. Requires treatment with a strong CYP3A4 inhibitor/inducer.
• • 12. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• • 13. Major surgical procedure within 30 days of the first dose of study intervention.