Actively Recruiting
A Prospective, Multicenter, Phase II Trial to Evaluate Zanubrutinib and Tislelizumab and Standard Care for Progressive Large B-cell Lymphoma After Anti-CD19 CAR-T Therapy
Led by University Health Network, Toronto · Updated on 2025-06-19
76
Participants Needed
1
Research Sites
87 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating treatments for adults with Large B-cell lymphoma who have experienced disease progression after receiving anti-CD19 CAR-T therapy. This phase II trial aims to assess the effectiveness of two drugs, zanubrutinib and tislelizumab, either alone or combined, compared to standard care in this group of patients who have already undergone multiple treatments. The study is divided into two parts: an initial safety run-in period and an expanded cohort phase. During the safety run-in, 10 patients will receive either zanubrutinib orally twice daily or tislelizumab intravenously every three weeks to assess safety and tolerability. If deemed safe, the expanded cohort will explore combining both drugs, with patients receiving tislelizumab intravenously every three weeks and zanubrutinib orally twice daily for up to 34 cycles, approximately two years. A standard of care arm will also be available, where treatment is given as per the investigator's discretion. Participants will undergo regular assessments including imaging to measure tumor response, laboratory tests, and monitoring for side effects throughout the treatment. The primary outcome is the overall response rate measured over two years, with secondary outcomes including duration of response, progression-free survival, event-free survival, and overall survival. Patients will continue in the study as long as they tolerate treatment without disease progression, and safety will be closely monitored throughout the trial duration.
CONDITIONS
Brief Title
A Study to Evaluate Zanubrutinib and Tislelizumab in Progressive Lymphoma Post CAR-T
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Able and willing to provide written informed consent and comply with the study protocol
- Radiologically measurable disease with at least one nodal lesion > 2.0 cm or extranodal lesion > 1.0 cm
- For intervention arm: measurable disease with more than one site
- Relapsed or refractory Large B-cell lymphoma after CD19 CAR-T therapy within 6 weeks prior to enrollment
- For intervention arm: hemoglobin ≥ 80 g/L at screening
- For intervention arm: platelet count ≥ 50 x 10^9/L at screening
- For intervention arm: neutrophil count ≥ 1.0 x 10^9/L at screening
- For intervention arm: performance status ≤ 2 at screening
- AST and ALT below 2.5 times upper limit of normal at screening
- Serum total bilirubin below 1.5 times upper limit of normal (or below 3 times in Gilbert's syndrome) at screening
- Creatinine clearance ≥ 30 mL/min at screening
You will not qualify if you...
- Life expectancy less than 30 days at enrollment
- Prior exposure to BTK or PD-1 inhibitors before enrollment
- History of anaphylactic reaction to monoclonal antibody therapy
- Use of prednisone over 10 mg daily for at least 7 days before trial treatment
- Uncontrolled autoimmune diseases
- Active central nervous system lymphoma involvement
- History of allogeneic or organ transplant
- Active bleeding disorders or recent severe bleeding events
- Difficulty swallowing oral medication or significant gastrointestinal issues limiting absorption
- Active uncontrolled infections or positive serologic status for hepatitis B or C without proper control
- Uncontrolled serious illnesses including significant heart, lung, or cerebrovascular conditions
- Other active malignancies within 2 years except certain localized cancers
- Female patients must use effective contraception during and 90 days after treatment
- Male patients must use barrier contraception or be vasectomized during and 90 days after treatment
- Major surgery within 4 weeks before starting study drug
- Live vaccines within 28 days prior to starting study drug
- Treatment with warfarin or vitamin K antagonists
- Severe pulmonary disease or history of interstitial lung disease
- Active symptomatic infections or human T-cell lymphotropic virus type 1 positivity
- Any condition that may affect safety or study evaluation
- Active or history of severe autoimmune diseases except some controlled conditions
- Systemic treatment with corticosteroids or immunosuppressive drugs within 14 days except for CNS lymphoma
- Live vaccines within 28 days of screening
- Contraindications for zanubrutinib use
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Until early safety interim analysis after 2 cycles of monotherapy
Participants receive either tislelizumab or zanubrutinib monotherapy to evaluate safety and tolerability before combination therapy.
Repeated visits every 3 weeks for each treatment cycle
Duration - Up to 34 cycles (~2 years) of treatment as long as toxicity is acceptable and disease does not progress
Participants receive combination therapy with tislelizumab and zanubrutinib or continue monotherapy depending on the study phase and safety results.
Visits every 3 weeks corresponding with each treatment cycle
Trial Site Locations
Total: 1 location
1
University Health Network (UHN)
Toronto, Ontario, Canada, M5G 2M9
Actively Recruiting
Research Team
J
John Kuruvilla, FRCPC
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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