MAVRiC studies 2L treatment with AV in patients with CLL/SLL who have relapsed after a course of BTKi + BCL2i combination, with and without Obinutuzumab

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 May 2026 → ongoing

Decision date (initial)

2026-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-518858-17-00

ClinicalTrials.gov

NCT07024706

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To determine the efficacy of second-line (2L) treatment with acalabrutinib plus venetoclax (AV) after relapse following first-line (1L) covalent Bruton’s tyrosine kinase inhibitor (cBTKi) + B-cell leukemia/lymphoma-2 inhibitor (BCL2i) by assessment of overall response rate (ORR) in participants with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL)

Secondary objectives 7

1. 1) Efficacy: To determine the efficacy of 2L treatment with AV after relapse by assessment of progression-free survival (PFS)
2. 2) Efficacy: To determine the efficacy of 2L treatment with AV after relapse by assessment of duration of response (DoR)
3. 3) Efficacy: To determine the efficacy of 2L treatment with AV after relapse by assessment of event-free survival (EFS)
4. 4) Efficacy: To determine the efficacy of 2L treatment with AV after relapse by assessment of time to next treatment (TTNT)
5. 5) Efficacy: To determine the efficacy of treatment with AV after relapse by assessment of overall survival (OS)
6. 6) Efficacy: To determine the efficacy of 2L treatment with AV after relapse by assessment of undetectable minimal residual disease (uMRD)
7. 7) Safety: To assess the safety and tolerability of 2L treatment with AV after relapse following 1L cBTKi + BCL2i in participants with CLL/SLL

Conditions and MedDRA coding

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Participant must be ≥ 18 years at the time of signing informed consent.
2. 2. Diagnosis of CLL/SLL according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines 2018 (Hallek et al. 2018)
3. 3. Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ partial remission (PR) (i.e., complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or PR) with a minimum of 2 years since the end of the prior 1L treatment.
4. 4. The following data must be available or at least the appropriate samples drawn/acquired prior to dosing: a) variable region of immunoglobulin heavy chain (IGHV) (mutated vs. unmutated) b) 17p deletion [del(17p)] (present or absent) c) Tumor protein 53 (TP53) mutation (present or absent)
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
6. 6. Adequate organ and bone marrow (BM) function.

Exclusion criteria 13

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR, defined as the proportion of participants who achieve best response of complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria (Hallek et al, 2018) as assessed by the investigator, with timepoint of primary interest after completion of Cycle 14.

Secondary endpoints 7

1. 1) Efficacy: PFS, defined as time from date of the first dose until progression per iwCLL criteria (Hallek et al, 2018) as assessed by the investigator, or death due to any cause in the absence of progression. The measure of interest is the median of PFS.
2. 2) Efficacy: DoR, defined as the time from the date of first documented response until date of documented progression per iwCLL criteria (Hallek et al, 2018) as assessed by the investigator, or death due to any cause. The measure of interest is the median of DoR.
3. 3) Efficacy: EFS, defined as the time from date of the first dose until the first occurrence of disease progression, initiation of subsequent CLL/SLL therapy, or death due to any cause. The measure of interest is the median of EFS.
4. 4) Efficacy: TTNT, defined as the time from date of the first dose to the initiation of subsequent CLL/SLL therapy or death due to any cause. The measure of interest is the median of TTNT
5. 5) Efficacy: OS, defined as the time from date of the first dose until the date of death due to any cause. The timepoint of interest is the landmark estimate of OS at 5 years.
6. 6) Efficacy: Rate of peripheral blood (PB) uMRD, defined as proportion of participants achieving remission based on a clonoSEQ® assay result of < 1 CLL cell per 100,000 leukocytes (< 10^-5). The timepoint of interest is the rate of uMRD at 3 months after last treatment dose
7. 7) Safety: Safety and tolerability will be evaluated in terms of adverse event (AE)s/serious adverse event (SAE)s, AEs leading to treatment discontinuation and deaths, event(s) of clinical interest (ECI)s and relevant clinical laboratory results

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

6 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 100 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications