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

Sponsor: AstraZeneca

Sponsor score: 40

ClinicalTrials ID:NCT07024706

This Phase 2 study assesses the efficacy and safety of acalabrutinib plus venetoclax in relapsed CLL/SLL patients post-1L cBTKi+BCL2i therapy. Eligible participants are ≥18, with prior ≥PR response for 2 years, and specific genetic markers. The study includes screening, treatment, and follow-up, with participants grouped by disease risk. Acalabrutinib and venetoclax target BTK and BCL-2 pathways, respectively.

Patient Parameters

Program Overview

This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, and have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment.

Description

The purpose of this study is to explore the use of second line (2L) treatment with AV after relapse following first line (1L) cBTKi + BCL2i by assessment of ORR in participants with CLL/SLL. This study will generate efficacy and safety data needed to understand outcomes associated with AV in patients who initially responded with partial remission (PR) or better for a minimum of 2 years from the end of 1L cBTKi + BCL2i combination treatment and are experiencing clinical relapse requiring further treatment. MAVRiC explores AV as second-line (2L) CLL/SLL treatment after relapse on first-line (1L) cBTKi + BCL-2 by assessment of overall response rate (ORR)

  • The study duration for each participant will be up to 5 year.
  • The study consists of screening, treatment, and post-intervention follow-up periods.
  • Participants will be grouped into low or high risk cohorts based on disease risk determined by IGHV mutation and TP53 aberrancy.

Eligibility Criteria

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.

Locations

FACILITYZIPCITYSTATE
Research Site02215BostonMassachusetts
Research Site28204CharlotteNorth Carolina
Research Site28204CharlotteNorth Carolina
Research Site27705DurhamNorth Carolina
Research Site27103Winston-SalemNorth Carolina

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