Sonrotoclax Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma Planned for Standard of Care CAR-T Cell Therapy

May 11, 2026 updated by: Canadian Cancer Trials Group

A Phase II Study of Sonrotoclax Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma Planned for Standard of Care CAR-T Cell Therapy

The purpose of this study is to evaluate the effects of adding two oral medications (sonrotoclax plus zanubrutinib) to standard of care chimeric antigen receptor (CAR-T) cell therapy in participants with mantle cell lymphoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Combining sonrotoclax (a next-generation BCL-2 inhibitor) with zanubrutinib (a selective BTK inhibitor) in mantle cell lymphoma (MCL)-is expected to be driven by strong biologic synergy, complementary mechanisms, and more durable responses without chemotherapy. Patients participating in this study must already be planning, and be eligible for CAR-T cell therapy outside of this protocol. CAR-T will be administered according to local or provincial guidelines.

If a patient decides to take part in this study, the patient will first get zanubrutinib (if not on it before starting the study), then during the induction phase they will get a combination of sonrotoclax (with a ramp-up dosing schedule) plus zanubrutinib followed by CAR-T cell therapy, followed zanubrutinib alone/ maintenance.

After finishing study treatment, and even if patients stop treatment early, the study doctor will continue to follow the patient's condition for the rest of their life or until all study results are known

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Not yet recruiting
        • BCCA - Vancouver
        • Contact:
          • Diego Villa Restrepo
          • Phone Number: 2740 604 877-6000
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • University Health Network
        • Contact:
          • Sita Bhella

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have histologically confirmed mantle cell lymphoma that is relapsed or refractory after at least one prior line of systemic therapy
  • Eligible for and planned to receive Health Canada approved CAR-T.
  • Have a formalin fixed paraffin embedded tumour tissue block available and must have provided informed consent for the release of the block.
  • Presence of radiologically documented disease.
  • Measurable disease (one site bidimensionally measurable).
  • Age ≥ 18 years.
  • Have an ECOG performance status of 0, 1 or 2
  • Anticipated life expectancy of ≥ 6 months
  • Adequate hematologic and biochemical parameters
  • Must have received prior systemic therapy as shown below;
  • At least one line of systemic therapy including a Bruton's Tyrosine Kinase inhibitor (BTKi).
  • Participants who have previously received venetoclax, sonrotoclax, or any other BCL2 inhibitor (BCL2i) are eligible as long as progressive disease did not occur within 6 months of the last dose of BCL2i. Participants with progressive disease during BCL2i therapy or within 6 months of last dose are not eligible.
  • Participants must enter the study while on a BTKi or enroll to a substudy of the protocol to receive zanubrutinib for a minimum duration prior to enrolling to the main study.
  • Participants previously exposed to zanubrutinib are eligible irrespective of response to treatment.
  • Participants entering the study while on a BTKi must have their BTKi switched to zanubrutinib supplied through the study.
  • Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior therapies.
  • Adequate washout must be followed per protocol.
  • Prior high-dose myelosuppresive radiation is permitted ≥28 prior to enrollment.
  • Previous major surgery is permitted ≥28 days prior to enrollment. Participants of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria

  • • Participants on active anticancer therapy for other advanced or metastatic malignancies.
  • Concurrent treatment with other anti-cancer therapy
  • Serious illnesses or medical conditions which would not permit the participant to be managed according to the protocol.
  • Known hypersensitivity to the study drug(s) or their components.
  • Prior CD19-directed CAR-T at any time, autologous hematopoietic cell transplantation within 6 weeks, or allogeneic hematopoietic cell transplantation within 3 months. Allogeneic hematopoietic cell transplantation recipients must be free of clinically-significant graft-versus-host disease (GvHD) and must be off immunosuppression for GvHD for at least 4 weeks before enrollment.
  • Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction (including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or unstable angina congestive heart failure or myocardial infarction within the previous year.
  • Active, uncontrolled bacterial, fungal, or viral infection within 14 days prior to enrollment
  • Pregnant or breastfeeding women.
  • Inability to discontinue use of moderate or strong CYP3A inducers or inhibitors during the ramp-up treatment period with sonrotoclax.
  • Live vaccination within 4 weeks prior to enrollment or who plan to receive a live vaccine during treatment or within 90 days post last dose.
  • Inability to swallow capsules or tablets or have any diseases significantly affecting GI function
  • Active central nervous system (CNS) disease; Participants with stable CNS disease are eligible.
  • Growth factors within 28 days prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zanubrutinib + Sonrotoclax
Drug: Zanubrutinib
assigned at enrollment
Drug: Sonrotoclax
assigned at enrollment
Biological: CAR-T Cell Therapy
Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete response post CAR-T
Time Frame: 3.5 years
3.5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 4 years
4 years
Objective Response Rate assessed by the Lugano Classification
Time Frame: 3.5 years
3.5 years
1 year Progression-Free Survival
Time Frame: 4 years
4 years
Number and Severity of Adverse Events
Time Frame: 3.5 years
3.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Canadian Cancer Trials Group

Collaborators

BeOne Medicines

Investigators

  • Study Chair: Diego Villa, BCCA-Vancouver Cancer Centre
  • Study Chair: Robert Puckrin, Tom Baker Cancer Centre, Calgary, AB Canada

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 30, 2026

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

January 6, 2026

First Submitted That Met QC Criteria

January 6, 2026

First Posted (Actual)

January 14, 2026

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I245

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Sharing Access Criteria

As per CCTG policies

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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