Clinical trial NCT07024706: Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab
Official title: The MAVRiC Study: A Phase II Study of Disease Risk Mutation Guided Finite Duration Acalabrutinib Plus Venetoclax for Relapse in CLL/SLL After First-line Finite Covalent BTKi Plus BCL2i Combination, With or Without Obinutuzumab
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Relapsed CLL
Refractory CLL
Acalabrutinib
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
name: Genentech, Inc.
First posted: 2025-06-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: ORR assessed at multiple timepoints during treatment period (each cycle is 28 days). Timepoint for primary analysis is at completion of cycle 14
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
measure: Duration of Response (DoR)
timeFrame: DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
measure: Event Free Survival (EFS)
timeFrame: EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
measure: Time to Next Treatment (TTNT)
timeFrame: TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
measure: Overall Survival (OS)
timeFrame: OS will be assessed every 3 months through the study completion, for 5 years
measure: Rate of undetectable Minimal Residual Disease (uMRD)
timeFrame: uMRD will be measured at 3 months after last treatment
measure: Treatment-Emergent Adverse Events (safety and tolerability) of second-line (2L) treatment with Acalabrutinib and Venetoclax after relapse following 1L cBTKi + BCL2i
timeFrame: Safety and tolerability will be evaluated throughout the study for 5 years
Other outcomes:
Locations:
Study officials:
References: