Recruiting NCT07024706

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

Phase II Interventional Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Acalabrutinib, Venetoclax.
Who it may be relevant to: Registry conditions: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL). Basic parameters: 18 years — 130 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Austria, Brazil, Czechia, Ireland +3
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

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.

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.

Interventions

Drug Acalabrutinib
Acalabrutinib is an orally available cBTKi that inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway.
Drug Venetoclax
Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein BCL-2

Primary outcome measures

Overall Response Rate (ORR) [Time frame: ORR assessed at multiple timepoints during treatment period (each cycle is 28 days). Timepoint for primary analysis is at completion of cycle 14]

Secondary outcome measures (7)

Progression Free Survival (PFS) [Time frame: PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
Duration of Response (DoR) [Time frame: DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
Event Free Survival (EFS) [Time frame: EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
Time to Next Treatment (TTNT) [Time frame: TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
Overall Survival (OS) [Time frame: OS will be assessed every 3 months through the study completion, for 5 years]
Rate of undetectable Minimal Residual Disease (uMRD) [Time frame: uMRD will be measured at 3 months after last treatment]
Treatment-Emergent Adverse Events (safety and tolerability) of second-line (2L) treatment with Acalabrutinib and Venetoclax after relapse following 1L cBTKi + BCL2i [Time frame: Safety and tolerability will be evaluated throughout the study for 5 years]

Eligibility criteria

Main Inclusion Criteria:

Participant must be ≥ 18 years at the time of signing informed consent.
Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)
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.
The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:

IGHV (mutated vs. unmutated)
del(17p) (present or absent)
TP53 mutation (present or absent)
ECOG performance status 0, 1 or 2
Adequate organ and bone marrow (BM) function.

Main Exclusion Criteria:

Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
Significant cardiovascular or cerebrovascular disease.
Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
Child-Pugh B/C liver cirrhosis.
History of prior or current malignancy.
HIV positive
History of progressive multifocal leukoencephalopathy (PML).
Active hepatitis B or C infection:
Corticosteroid use > 20 mg within 1 week before the first dose of study intervention.
History of hypersensitivity or anaphylaxis to study intervention(s).
Requires treatment with a strong CYP3A4 inhibitor/inducer.
Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
Major surgical procedure within 30 days of the first dose of study intervention.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Non-randomized
Model: Single group
Masking: Open label
Primary purpose: Treatment

Study locations

Italy · 7 centers

Research Site — Meldola
Research Site — Milan
Research Site — Milan
Research Site — Padua
Research Site — Ravenna
Research Site — Rome
Research Site — Torino

Spain · 7 centers

Research Site — Barcelona
Research Site — Barcelona
Research Site — Granada
Research Site — Madrid
Research Site — Madrid
Research Site — Madrid
Research Site — Majadahonda

Poland · 6 centers

Research Site — Bydgoszcz
Research Site — Krakow
Research Site — Lodz
Research Site — Lublin
Research Site — Warsaw
Research Site — Warsaw

United States · 5 centers

Research Site — Boston
Research Site — Charlotte
Research Site — Charlotte
Research Site — Durham
Research Site — Winston-Salem

Brazil · 5 centers

Research Site — Goiânia
Research Site — Porto Alegre
Research Site — Porto Alegre
Research Site — São Paulo
Research Site — São Paulo

Czechia · 3 centers

Research Site — Brno
Research Site — Hradec Kralova
Research Site — Ostrava

Ireland · 2 centers

Research Site — Dublin
Research Site — Dublin

Austria · 1 center

Research Site — Horn

Identifiers

NCT: NCT07024706 · D8220C00036

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗