Chronic Lymphocytic Leukemia (CLL)Phase 2MAVRiCNCT07024706
MAVRiC Studies 2L Treatment With AV in Patients With CLL/SLL Who Have Relapsed After a Course of BTKi + BCL2i Combination, With or Without Obinutuzumab
A Phase 2 study testing Acalabrutinib and Venetoclax in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by AstraZeneca at 47 sites in 9 countries.
Trial summary
This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, who have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
- What is being tested?
- Acalabrutinib and Venetoclax
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 47 sitesin 9 countries
- Study dates
- 4 Jun 2026to 23 Mar 2033
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Participant must be ≥ 18 years at the time of signing informed consent.
- Diagnosis of relapsed CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018) in need of treatment.
- Participants must have received only one prior first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) for 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.
Trial locations and contacts
47 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
47 sites in 9 countries
Spain10 sites, 10 recruiting
- Recruiting
Research Site
Barcelona, 08041
- Recruiting
Research Site
Barcelona, 8035
- Recruiting
Research Site
Granada, 18014
- Recruiting
Research Site
Madrid, 28031
- Recruiting
Research Site
Madrid, 28034
- Not yet recruiting
Research Site
Madrid, 28041
- Recruiting
Research Site
Majadahonda, 28222
- Not yet recruiting
Research Site
Oviedo, 33011
- Not yet recruiting
Research Site
Seville, 41013
- Not yet recruiting
Research Site
Zaragoza, 50 012
Italy8 sites, 5 recruiting
- Recruiting
Research Site
Meldola, 47014
- Not yet recruiting
Research Site
Milan, 20132
- Withdrawn
Research Site
Milan, 20132
- Not yet recruiting
Research Site
Milan, 20162
- Recruiting
Research Site
Padua, 35128
- Recruiting
Research Site
Ravenna, 48121
- Withdrawn
Research Site
Rome, 00168
- Withdrawn
Research Site
Torino, 10126
United Kingdom7 sites, 7 recruiting
- Not yet recruiting
Research Site
Colchester, CO4 5JL
- Not yet recruiting
Research Site
Derby, DE22 3NE
- Not yet recruiting
Research Site
Edgbaston, B15 2WB
- Not yet recruiting
Research Site
Exeter, EX2 5DW
- Not yet recruiting
Research Site
Leeds, LS8 1NT
- Not yet recruiting
Research Site
London, SE5 9RS
- Not yet recruiting
Research Site
Southampton, SO166YD
Poland6 sites, 4 recruiting
- Not yet recruiting
Research Site
Bydgoszcz, 85-168
- Withdrawn
Research Site
Krakow, 30-727
- Withdrawn
Research Site
Lodz, 93-513
- Not yet recruiting
Research Site
Lublin, 20-090
- Not yet recruiting
Research Site
Warsaw, 02-172
- Not yet recruiting
Research Site
Warsaw, 02-776
United States5 sites, 4 recruiting
- Recruiting
Research Site
Boston, Massachusetts, 02215
- Withdrawn
Research Site
Charlotte, North Carolina, 28204
- Recruiting
Research Site
Charlotte, North Carolina, 28204
- Recruiting
Research Site
Durham, North Carolina, 27705
- Recruiting
Research Site
Winston-Salem, North Carolina, 27103
Brazil5 sites, 5 recruiting
- Not yet recruiting
Research Site
Goiânia, 74605-020
- Not yet recruiting
Research Site
Porto Alegre, 90035-903
- Not yet recruiting
Research Site
Porto Alegre, 90110-270
- Not yet recruiting
Research Site
São Paulo, 01246-000
- Not yet recruiting
Research Site
São Paulo, 1409
Czechia3 sites, 3 recruiting
- Not yet recruiting
Research Site
Brno, 625 00
- Not yet recruiting
Research Site
Hradec Kralova, 50005
- Not yet recruiting
Research Site
Ostrava, 708 502
Ireland2 sites, 2 recruiting
- Recruiting
Research Site
Dublin, 7
- Recruiting
Research Site
Dublin, D08 NHY1
About this study
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
This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, who have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment.
Read the 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.
- Being tested
- Acalabrutinib, Venetoclax
- Keywords
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Relapsed CLL, Refractory CLL, Acalabrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called CALQUENCE®
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.
VenetoclaxDrug
Also called Venclexta®, Venclyxto®
Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein BCL-2
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib and Venetoclax | Experimental | For Cohort 1, each participant will be in the study for approximately 5 years (60 months) counting from C1D1, starting with 2 cycles of acalabrutinib lead-in treatment, followed by 12 cycles of AV combination treatment, and 4 years of follow-up.
For Cohort 2, each participant will be in the study for approximately 5 years (60 months) counting from C1D1 starting with 2 cycles of acalabrutinib lead-in treatment, followed by 22 cycles of AV combination treatment, and 3 years of follow-up. Receives: Drug: Acalabrutinib; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR, defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per iwCLL criteria as assessed by the investigator.
Measured: ORR assessed at multiple timepoints during treatment period (each cycle is 28 days) and then every 12 months through the study completion, for 5 years. Timepoint for primary analysis is at completion of cycle 14.
Secondary outcomes (7)
Progression Free Survival (PFS)
PFS is defined as time from date of the first dose until progression per iwCLL criteria or death due to any cause in the absence of progression.
Measured: PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days), and then at regular intervals through the study completion, for 5 years.
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per iwCLL criteria or death due to any cause.
Measured: DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days), and then at regular intervals through the study completion, for 5 years.
Event Free Survival (EFS)
EFS is defined as the time from date of the first dose until the first occurrence of disease progression per iwCLL criteria, initiation of subsequent CLL/SLL therapy, or death due to any cause.
Measured: EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days), and then at regular intervals through the study completion, for 5 years.
Time to Next Treatment (TTNT)
TTNT is defined as the time from date of the first dose to the initiation of subsequent CLL/SLL therapy or death due to any cause.
Measured: TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days), and then at regular intervals through the study completion, for 5 years.
Overall Survival (OS)
OS is defined as the time from date of the first dose until the date of death due to any cause.
Measured: OS will be assessed every 3 months through the study completion, for 5 years.
Rate of undetectable Minimal Residual Disease (uMRD)
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).
Measured: uMRD will be measured annually until disease progression. Timepoint of interest is the rate of uMRD at 3 months after last treatment dose.
Treatment-Emergent Adverse Events (safety and tolerability) of second-line (2L) treatment with Acalabrutinib and Venetoclax after relapse following 1L cBTKi + BCL2i
Safety and tolerability will be evaluated in terms of AEs/SAEs, AEs leading to treatment discontinuation, events(s) of clinical interests and relevant clinical laboratory results.
Measured: Safety and tolerability will be evaluated throughout the study for 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2025
- Study start4 Jun 2026
- Primary completion1 May 2029 (estimated)
- Study completion23 Mar 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AbbVie, Genentech, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07024706
- Sponsor's protocol ID
- D8220C00036
- Other IDs
- 2024-518858-17-00
- Acronym
- MAVRiC
- Status last verified
- Oct 2026
- First submitted
- 26 May 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Publications
Castonguay M, Anderson MA, Thompson P, Seymour JF. Venetoclax retreatment in chronic lymphocytic leukemia is biologically rational and clinically effective. Blood Adv. 2026 May 26;10(10):3357-3366. doi: 10.1182/bloodadvances.2026019871.
PubMed 41843779