A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma

NCT05951959 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: D822GC000012023-505205-16-00
• Study Type: interventional
• Target: 108
• Locations: 7 countries
• Sites: 29

Brief Summary

TrAVeRse is a multicentre, open-label, Phase II study of AVR in treatment naïve MCL participants. The primary objective will be to assess the rate of MRD-negative CR at end of induction after completing 13 cycles of AVR. Participants achieving an MRD-negative CR at the end of AVR induction will be randomised to continued acalabrutinib or observation. Participants who progress during observation may receive retreatment with acalabrutinib

Conditions

Mantle Cell Lymphoma (MCL)

Keywords

Mantle Cell Lymphoma; Lymphoma; Acalabrutinib; Venetoclax; Rituximab

Outcome Measures

Primary Outcomes (1)

• MRD-negative CR rate

  MRD-negative CR rate is defined as the proportion of participants who achieved MRD-negativity in peripheral blood by NGS at a threshold of 10-5 while in CR per the Lugano Classification for NHL at the end of AVR induction

  At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)

Secondary Outcomes (12)

• MRD-negative CR rate

  Up to approximately 67 months

• Overall Response Rate (ORR)

  Up to approximately 67 months

• Overall Response Rate (ORR)

  At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)

• Complete Response (CR) rate

  Up to approximately 67 months

• Complete Response (CR) rate

  At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)

Study Arms (1)

Acalabrutinib + Venetoclax + Rituximab

EXPERIMENTAL

Acalabrutinib + Venetoclax + Rituximab (AVR)

Drug: Acalabrutinib; Drug: Venetoclax; Drug: Rituximab

Interventions

Acalabrutinib DRUG

Investigational Product

Also known as: Acalabrutinib, CALQUENCE

Acalabrutinib + Venetoclax + Rituximab

Venetoclax DRUG

Investigator Product

Acalabrutinib + Venetoclax + Rituximab

Rituximab DRUG

Investigator Product

Acalabrutinib + Venetoclax + Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age
• Participant must be ≥ 18 years or the legal age of consent in the jurisdiction in which the study is taking place, whichever is greater, at the time of signing the informed consent.
• Type of Participant and Disease Characteristics
• Histologically documented MCL based on criteria established by the World Health Organization with documentation of chromosomal translocation t(11;14) (q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (e.g., CD5, CD19, CD20 or PAX5).
• Clinical Stage II, III, or IV by Ann Arbor Classification and requiring systemic treatment in the opinion of the treating clinician.
• At least 1 measurable site of disease per Lugano Classification for NHL (Appendix K). The site of disease must be \> 1.5 cm in the long axis regardless of short axis measurement or \> 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions, as assessed by diagnostic quality CT (MRI may be used for participants who are either allergic to CT contrast media or have renal insufficiency that per institutional guidelines restricts the use of CT contrast media).
• OR Participant with leukemic non-nodal MCL presentation with splenomegaly (spleen \>13 cm in length cranial to caudal) and Bone Marrow (BM) involvement.
• Eastern Cooperative Oncology Group PS of 0, 1, or 2 and ECOG PS of 3 if poor PS is due to lymphoma.
• Confirmed availability of sufficient FFPE tumour samples for central laboratory genomic profiling, including TP53 and clone identification for MRD testing per clonoSEQ® assay. Participants with leukemic non-nodal MCL may be enrolled with available BM tissue. For non-nodal leukaemic MCL participants and when nodal or extranodal tissue is not easily accessible and an invasive biopsy will cause a significant risk to the participant, the participant can be enrolled without a tissue biopsy if MCL BM involvement is confirmed by a BM biopsy and sufficient BM biopsy and aspirate provided for TP53 testing, tumour profiling and clone identification for MRD testing.
• Adequate organ and bone marrow function.
• Sex and Contraceptive/Barrier Requirements 8 Male and/or female Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants:
• \- Male participants with a female partner of child-bearing potential should use a condom from enrolment, throughout the study until 90 days following the last dose of venetoclax or rituximab, whichever is longer.
• For non-pregnant potentially childbearing partners, contraception recommendations should also be considered. A male participant must agree to refrain from sperm donation throughout the study until 90 days following the last dose of venetoclax or rituximab, whichever is longer.
• Female participants:

You may not qualify if:

• Medical Conditions
• Active CNS involvement by lymphoma or leptomeningeal disease
• Current or previous active malignancies requiring anticancer therapy except:
• \- adequately treated basal cell or squamous cell skin cancer
• \- in situ cancer
• \- history of cancer with no evidence of recurrence for ≥ 2 years before enrolment
• \- local radiotherapy with a field that does not overlap with sites of current MCL disease and given at least 3 months prior to the screening PET-CT scan and the participant had recovered from any associated toxicity.
• \- anti-hormonal therapies are permitted after discussion with the sponsor's medical monitor
• Participants for whom the goal of therapy is tumour debulking before ASCT
• Any severe or life-threatening illness, medical condition (e.g., uncontrolled hypertension, bleeding diathesis), or organ system dysfunction which, in the investigator' opinion, could compromise the participant safety, interfere with the absorption or metabolism of study intervention (acalabrutinib, rituximab, venetoclax) or put the study outcomes at undue risk
• Clinically significant cardiovascular disease such as uncontrolled or untreated symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, or QTc \> 480 msec at screening. Exception: Participants with controlled, asymptomatic atrial fibrillation during screening may enroll.
• Any active uncontrolled infection (bacterial, viral, fungal, or other infection including tuberculosis), defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment, which in the investigator's opinion makes it undesirable or pose a safety risk for the participant to participate in the study.
• HIV infection. As per standard of care, results of HIV serology should be known prior to start of study intervention. In the acute situation, registration may occur without the results of the HIV serology but must be available prior to start of study intervention
• Excluded Participants: Participants with active HIV infection (i.e., with detectable viral load by PCR) are excluded.
• Included Participants: HIV-positive participants receiving anti-retroviral treatment with undetectable viral load by PCR may be enrolled following discussion with the participant's HIV physician and the sponsor medical monitor. Potential interactions between anti-retroviral medications and study interventions should be considered.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (29)

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

Stony Brook, New York, 11794, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Heidelberg, 3084, Australia

Location

Research Site

Kogarah, NSW 2217, Australia

Location

Research Site

Nedlands, 6009, Australia

Location

Research Site

Sydney, 2109, Australia

Location

Research Site

Porto Alegre, 90035-003, Brazil

Location

Research Site

Rio de Janeiro, 22061-080, Brazil

Location

Research Site

São Paulo, 01401-002, Brazil

Location

Research Site

São Paulo, 05403-010, Brazil

Location

Research Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Research Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Research Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

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Barrie, Ontario, L4M 6M2, Canada

Location

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Toronto, Ontario, M5G 2M9, Canada

Location

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Montreal, Quebec, H3T 1E2, Canada

Location

Research Site

Gdynia, 81-519, Poland

Location

Research Site

Krakow, 30-727, Poland

Location

Research Site

Warsaw, 02-781, Poland

Location

Research Site

Madrid, 28041, Spain

Location

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Birmingham, B9 5SS, United Kingdom

Location

Research Site

Gloucester, GL1 3NN, United Kingdom

Location

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London, SW3 6JJ, United Kingdom

Location

Research Site

Norwich, NR4 7UY, United Kingdom

Location

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Nottingham, NG5 1PB, United Kingdom

Location

Research Site

Plymouth, PL68BQ, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma

Interventions

acalabrutinib; venetoclax; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase II, open-label, multicentre, international study assessing the efficacy of acalabrutinib in combination with venetoclax and rituximab in adult participants with treatment naïve MCL. Approximately 100 participants with treatment naïve MCL will be treated. The primary objective is to estimate the efficacy of AVR by assessment of CR rate with MRD negativity in participants with treatment naïve MCL.

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: July 19, 2023
• Study Start: December 13, 2023
• Primary Completion (Estimated): July 7, 2028
• Study Completion (Estimated): July 7, 2028
• Last Updated: October 21, 2025

Record last verified: 2025-10

Locations

CA (6); ES (1); GB (6); AU (4); US (5); BR (4); PL (3)