Mantle Cell Lymphoma (MCL)Phase 2TrAVeRseNCT05951959
A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma
A Phase 2 study testing Acalabrutinib, Venetoclax and Rituximab in people with Mantle Cell Lymphoma (MCL), run by AstraZeneca at 29 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle Cell Lymphoma (MCL)
- What is being tested?
- Acalabrutinib, Venetoclax and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 29 sitesin 7 countries
- Study dates
- 13 Dec 2023to 31 Oct 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 19Show fewer
- 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:
- Women of childbearing potential must have negative serum pregnancy test result prior to the start of study intervention (Cycle 1 Day 1) and agree to abstain from breastfeeding during study participation and at least 12 months after the last drug administration.
- Female participants of childbearing potential who are sexually active with a nonsterilized male partner must agree to use at least one highly effective form of birth control from enrolment, throughout the study and at least 2 days after the last dose of acalabrutinib, at least 6 months after the last dose of venetoclax, and at least 12 months after the last dose of rituximab, whichever is longer.
- Informed Consent 9 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Informed consent may be given either by the participant or their legally authorised representative.
- 10 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative.
Who cannot join
- 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
Show all 41Show fewer
- 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.
- Serologic status reflecting active hepatitis B or C. As per standard of care, results of hepatitis serology should be known prior to start of study intervention. In the acute situation, enrolment may occur without the results of the hepatitis serology but must be available prior to start of study intervention.
- Participants who are HBsAg positive or HBV-DNA PCR positive will not be eligible. Participants who are anti-HBc IgG antibody positive and who are HBsAg negative will need to have a negative PCR result before enrolment. Participants who have protective titres of HBsAb after vaccination will be eligible.
- Participants who are hepatitis C antibody positive and are HCV-PCR positive will not be eligible.
- History or ongoing confirmed progressive multifocal leukoencephalopathy.
- History of stroke or intracranial haemorrhage within 6 months prior to the first dose of study intervention (Cycle 1 Day 1).
- Uncontrolled autoimmune haemolytic anaemia or idiopathic thrombocytopenic purpura.
- Active bleeding from a gastrointestinal ulcer, except incidental finding identified on endoscopy that is attributable to MCL
- Participants with a known hypersensitivity to acalabrutinib, venetoclax, or rituximab or any of the excipients of the product.
- Known allergy to uric acid lowering agents (e.g., xanthine oxidase inhibitors or rasburicase)
- Severe prior reactions to monoclonal antibodies
- Known glucose-6-phosphate dehydrogenase deficiency
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass or inability to swallow the formulated product (tablets).
- Currently pregnant (confirmed with positive pregnancy test) or breast feeding
- Prior/Concomitant Therapy
- Any prior therapies for the treatment of MCL with the exception of involved site radiotherapy given at least 3 months prior to screening PET-CT scan and where the radiotherapy field does not overlap areas of current disease activity.
- Requiring continued treatment with a strong CYP3A4 inhibitor/inducer or its use within 7 days prior to the first dose (Cycle 1 Day 1) of acalabrutinib or venetoclax 21 Requiring continued anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon). Exceptions are DOACs rivaroxaban, apixaban, edoxaban and dabigatran
- 22 Requiring ongoing immunosuppressive therapy, including systemic or enteric corticosteroids except:
- Topical or inhaled corticosteroids or low-dose oral steroids (≤ 20 mg of prednisone or equivalent per day) as a therapy for comorbid conditions
- Short courses of glucocorticoids in excess of 20 mg prednisone for no more than 14 days for comorbid conditions.
- Systemic use of corticosteroids as a pre-phase to control MCL manifestations (up to approximately 100 mg prednisolone or equivalent daily) for up to 10 days.
- 23 Received major surgery (excluding placement of vascular access or for diagnosis) within 28 days of first dose of study intervention (Cycle 1 Day 1) 24 Receipt of live, attenuated vaccine within 28 days before the first dose of study intervention (Cycle 1 Day 1).
- See Section 6.9, for lists of prohibited (Table 15) and restricted (Table 16) concomitant medications.
- Prior/Concurrent Clinical Study Experience 25 Concurrent participation in another therapeutic clinical trial or participation in another clinical study with an investigational product or investigational medicinal device within 30 days prior to first dose of study treatment (Cycle 1 Day 1).
- Other Exclusions 26 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- 27 Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
- 28 Previous enrolment in the present study.
Trial locations and contacts
29 sites in 7 countries.
29 sites in 7 countries
Canada6 sites
Research Site
Barrie, Ontario, L4M 6M2
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Halifax, Nova Scotia, B3H 2Y9
Research Site
Montreal, Quebec, H3T 1E2
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 4E6
United Kingdom6 sites
Research Site
Birmingham, B9 5SS
Research Site
Gloucester, GL1 3NN
Research Site
London, SW3 6JJ
Research Site
Norwich, NR4 7UY
Research Site
Nottingham, NG5 1PB
Research Site
Plymouth, PL68BQ
United States5 sites
Research Site
Cleveland, Ohio, 44195
Research Site
Hackensack, New Jersey, 07601
Research Site
Houston, Texas, 77030
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Stony Brook, New York, 11794
Australia4 sites
Research Site
Heidelberg, 3084
Research Site
Kogarah, NSW 2217
Research Site
Nedlands, 6009
Research Site
Sydney, 2109
Brazil4 sites
Research Site
Porto Alegre, 90035-003
Research Site
Rio de Janeiro, 22061-080
Research Site
São Paulo, 01401-002
Research Site
São Paulo, 05403-010
Poland3 sites
Research Site
Gdynia, 81-519
Research Site
Krakow, 30-727
Research Site
Warsaw, 02-781
About this study
Official title: A Multicentre, Phase II, Open-label Study to Evaluate the Efficacy of Acalabrutinib in Combination With Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma (TrAVeRse)
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
Read the detailed description
Most mantle cell lymphoma (MCL) patients require treatment at diagnosis. Currently, despite the availability of a number of chemo-immunotherapy-based frontline treatment options, there is no clear superior regimen or curative option for MCL patients. This study aims to evaluate the efficacy of a chemotherapy-free triplet combination regimen of a Bruton's Tyrosine Kinase-inhibitor (acalabrutinib), a BCL2 inhibitor (venetoclax) and an anti-CD20 monoclonal antibody (rituximab) (AVR), in treatment naïve MCL participants.
The study will also assess the feasibility of response-adapted treatment cessation for participants who achieve minimal residual disease (MRD) negative complete response (CR) after AVR induction and the efficacy of retreatment with acalabrutinib in a subgroup of participants who relapse after stopping all anti-lymphoma therapy.
All participants are planned to receive 13 cycles of AVR induction. Each cycle is 28 days. During the induction phase, acalabrutinib is administered twice a day (bd) orally for a total of 13 cycles starting on Cycle 1, venetoclax is administered once daily orally for a total of 12 cycles starting on Cycle 2, and rituximab is administered intravenously on Day 1 of every cycle, for a total of 12 cycles starting on Cycle 1.
- Participants who complete 13 cycles of AVR induction will be centrally tested for MRD status at completion of Cycle 13 and will continue to receive acalabrutinib bd for one full additional cycle (Cycle 14) while awaiting the results of the centralized MRD assessment and evaluation of disease response.
- Participants whose status is MRD-negative CR at the end-of-Cycle 13 assessments will be randomised in a 1:1 ratio to acalabrutinib or observation starting at Cycle 15. Those randomised to acalabrutinib will continue to receive acalabrutinib until progressive disease (PD), death, or unacceptable toxicity whereas those randomised to observation will not receive any anti-lymphoma treatment while in observation. Among the latter group, participants who relapse while in observation may be retreated with acalabrutinib at the time of relapse.
- Participants whose status is MRD-positive CR, PR, or stable disease at the end-of-Cycle 13 assessments will continue to receive acalabrutinib until PD, death, or unacceptable toxicity. The total duration of the study will be approximately 67 months.
Objectives and Endpoints
Primary:
•To assess the efficacy of AVR by assessment of MRD-negative CR rate at the end of AVR induction, i.e., following completion of Cycle 13
Secondary:
- To assess the efficacy of AVR by assessment of MRD-negative CR rate at any time during the study
- To assess the efficacy of AVR by assessment of overall response rate (ORR), CR rate, duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS)
- To assess the efficacy of continued acalabrutinib treatment compared to observation, in participants achieving MRD-negative CR after AVR induction by assessment of post randomisation time to first occurrence of relapse or death, EFS, and TTNT
- To assess the safety and tolerability of AVR with continued acalabrutinib or observation until disease progression
- Conditions
- Mantle Cell Lymphoma (MCL)
- Being tested
- Acalabrutinib, Venetoclax, Rituximab
- Keywords
- Mantle Cell Lymphoma, Lymphoma, Acalabrutinib, Venetoclax, Rituximab
- Medical subject headings
- Lymphoma, Mantle-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called Acalabrutinib, CALQUENCE
Investigational Product
VenetoclaxDrug
Investigator Product
RituximabDrug
Investigator Product
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib + Venetoclax + Rituximab | Experimental | Acalabrutinib + Venetoclax + Rituximab (AVR) Receives: Drug: Acalabrutinib; Drug: Venetoclax; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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 any time during the study.
Measured: Up to approximately 67 months
Overall Response Rate (ORR)
ORR is defined as the proportion of participants with a CR or PR, as determined by the investigator.
Measured: Up to approximately 67 months
Overall Response Rate (ORR)
ORR is defined as the proportion of participants with a CR or PR, as determined by the investigator.
Measured: At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Complete Response (CR) rate
CR rate is defined as the proportion of participants with a best response of CR.
Measured: Up to approximately 67 months
Complete Response (CR) rate
CR rate is defined as the proportion of participants with a best response of CR.
Measured: At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Duration of Response (DoR)
The DoR is defined as the time from the date of first documented response (CR-PR) until the date of documented progression per the Lugano Classification for NHL or death (by any cause in the absence of disease progression), whichever occurs first.
Measured: Up to approximately 67 months
Time to Next Treatment (TTNT)
TTNT or death is defined as the time from the start of AVR induction until the start of the next anti-lymphoma therapy (including local radiotherapy, unless pre-planned at baseline) or death due to any cause, whichever comes first.
Measured: Up to approximately 67 months
Progression-free Survival (PFS)
PFS is defined as the time from the start of AVR induction until the date of documented objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy prior to progression.
Measured: Up to approximately 67 months
Event Free Survival (EFS)
EFS is defined as the time from the start of AVR induction to any of the following events: disease progression, or initiation of systemic anti-lymphoma treatment and or unplanned radiation, or death due to any cause, whichever occurs first.
Measured: Up to approximately 67 months
Overall Survival (OS)
OS is defined as the time from the start of AVR induction until death due to any cause.
Measured: Up to approximately 67 months
Post randomization time to first occurrence of relapse or death, EFS and TTNT in continued acalabrutinib arm compared to observation arm.
Time to first occurrence of relapse or death is defined as the time from Cycle 15 Day 1 until date of progression per the Lugano Classification for NHL as assessed by investigator, or death due to any cause, whichever occurs first.
Event-free survival is defined as the time from Cycle 15 Day 1 until any of the following events: disease progression, or initiation of subsequent systemic anti-lymphoma treatment and/or unplanned radiation, or death due to any cause, whichever occurs first.
Time to next therapy or death is defined as the time from Cycle 15 Day 1 until the start of the next anti-lymphoma therapy (including local radiotherapy, unless pre-planned at baseline) or death due to any cause, whichever comes first.
Measured: Yearly from Cycle 15 (each cycle is 28 days) Day 1, until 3 years after randomization
Number of participants with any Adverse Events (AE), Serious Adverse Events (SAE), Adverse Event of Special Interest (AESI) and AEs leading to study treatment discontinuation or dose modification.
Adverse events will be graded by the investigator according to the NCI-CTCAE v5.0. Each AE verbatim term will be coded to a system organ class and a preferred term using the MedDRA.
Measured: Up to approximately 67 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2023
- Study start13 Dec 2023
- Primary completion31 Oct 2028 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mantle Cell Lymphoma (MCL)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
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05951959
- Sponsor's protocol ID
- D822GC00001
- Other IDs
- 2023-505205-16-00, 2023
- Acronym
- TrAVeRse
- Status last verified
- Aug 2026
- First submitted
- 5 Jun 2023
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Phase II, Open-label Study to Evaluate the Efficacy of Acalabrutinib in Combination With Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma (TrAVeRse)
- ClinicalTrials.gov ID
- NCT05951959
- Acronym / sponsor ID
- TrAVeRse / D822GC00001
- Conditions
- Mantle Cell Lymphoma (MCL)
- Keywords
- Mantle Cell Lymphoma, Lymphoma, Acalabrutinib, Venetoclax, Rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 108 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 13 Dec 2023 (actual)
- Primary completion
- 31 Oct 2028 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 19 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Most mantle cell lymphoma (MCL) patients require treatment at diagnosis. Currently, despite the availability of a number of chemo-immunotherapy-based frontline treatment options, there is no clear superior regimen or curative option for MCL patients. This study aims to evaluate the efficacy of a chemotherapy-free triplet combination regimen of a Bruton's Tyrosine Kinase-inhibitor (acalabrutinib), a BCL2 inhibitor (venetoclax) and an anti-CD20 monoclonal antibody (rituximab) (AVR), in treatment naïve MCL participants.
The study will also assess the feasibility of response-adapted treatment cessation for participants who achieve minimal residual disease (MRD) negative complete response (CR) after AVR induction and the efficacy of retreatment with acalabrutinib in a subgroup of participants who relapse after stopping all anti-lymphoma therapy.
All participants are planned to receive 13 cycles of AVR induction. Each cycle is 28 days. During the induction phase, acalabrutinib is administered twice a day (bd) orally for a total of 13 cycles starting on Cycle 1, venetoclax is administered once daily orally for a total of 12 cycles starting on Cycle 2, and rituximab is administered intravenously on Day 1 of every cycle, for a total of 12 cycles starting on Cycle 1.
- Participants who complete 13 cycles of AVR induction will be centrally tested for MRD status at completion of Cycle 13 and will continue to receive acalabrutinib bd for one full additional cycle (Cycle 14) while awaiting the results of the centralized MRD assessment and evaluation of disease response.
- Participants whose status is MRD-negative CR at the end-of-Cycle 13 assessments will be randomised in a 1:1 ratio to acalabrutinib or observation starting at Cycle 15. Those randomised to acalabrutinib will continue to receive acalabrutinib until progressive disease (PD), death, or unacceptable toxicity whereas those randomised to observation will not receive any anti-lymphoma treatment while in observation. Among the latter group, participants who relapse while in observation may be retreated with acalabrutinib at the time of relapse.
- Participants whose status is MRD-positive CR, PR, or stable disease at the end-of-Cycle 13 assessments will continue to receive acalabrutinib until PD, death, or unacceptable toxicity. The total duration of the study will be approximately 67 months.
Objectives and Endpoints
Primary:
•To assess the efficacy of AVR by assessment of MRD-negative CR rate at the end of AVR induction, i.e., following completion of Cycle 13
Secondary:
- To assess the efficacy of AVR by assessment of MRD-negative CR rate at any time during the study
- To assess the efficacy of AVR by assessment of overall response rate (ORR), CR rate, duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS)
- To assess the efficacy of continued acalabrutinib treatment compared to observation, in participants achieving MRD-negative CR after AVR induction by assessment of post randomisation time to first occurrence of relapse or death, EFS, and TTNT
- To assess the safety and tolerability of AVR with continued acalabrutinib or observation until disease progression
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib + Venetoclax + Rituximab | Experimental | Drug: Acalabrutinib, Drug: Venetoclax, Drug: RituximabAcalabrutinib + Venetoclax + Rituximab (AVR) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (41 listed)
- Medical Conditions
- Active CNS involvement by lymphoma or leptomeningeal disease
- Current or previous active malignancies requiring anticancer therapy except:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: Acalabrutinib, CALQUENCEInvestigational Product | Drug | Acalabrutinib + Venetoclax + Rituximab |
| VenetoclaxInvestigator Product | Drug | Acalabrutinib + Venetoclax + Rituximab |
| RituximabInvestigator Product | Drug | Acalabrutinib + Venetoclax + Rituximab |
Primary outcome
MRD-negative CR rate
Time frame: At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
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
12 secondary outcomes
MRD-negative CR rate
Time frame: Up to approximately 67 months
Overall Response Rate (ORR)
Time frame: Up to approximately 67 months
Overall Response Rate (ORR)
Time frame: At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Complete Response (CR) rate
Time frame: Up to approximately 67 months
Complete Response (CR) rate
Time frame: At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)
Duration of Response (DoR)
Time frame: Up to approximately 67 months
Time to Next Treatment (TTNT)
Time frame: Up to approximately 67 months
Progression-free Survival (PFS)
Time frame: Up to approximately 67 months
Event Free Survival (EFS)
Time frame: Up to approximately 67 months
Overall Survival (OS)
Time frame: Up to approximately 67 months
Post randomization time to first occurrence of relapse or death, EFS and TTNT in continued acalabrutinib arm compared to observation arm.
Time frame: Yearly from Cycle 15 (each cycle is 28 days) Day 1, until 3 years after randomization
Number of participants with any Adverse Events (AE), Serious Adverse Events (SAE), Adverse Event of Special Interest (AESI) and AEs leading to study treatment discontinuation or dose modification.
Time frame: Up to approximately 67 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Mantle Cell Lymphoma (MCL)
Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer
Not yet recruitingPhase 2
A Study of Zanubrutinib, Obinutuzumab, and Sonrotoclax in People With Mantle Cell Lymphoma
Mantle Cell Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib, Venetoclax and Rituximab in people with Mantle Cell Lymphoma (MCL), run by AstraZeneca at 29 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Canada, United Kingdom, United States, Australia, Brazil and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRD-negative CR rate (time frame: At the end of AVR induction, i.e., following completion of Cycle 13 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.