Zanubrutinib + Tislelizumab for Lymphoma

(ZeTA Trial)

Overseen By John Kuruvilla, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: BTK inhibitors, PD-1 inhibitors

Disqualifiers: Autoimmune diseases, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

76 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase ll study of participants with large B Cell lymphoma previously treated with anti-CD19 Chimeric antigen receptor (CAR-T) therapy. The purpose of the study is to to evaluate the efficacy of zanubrutinib and tislelizumab in patients with progressive lymphoma post anti-CD 19 CAR-T failure.

Research Team

John Kuruvilla, FRCPC

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 with large B-cell lymphoma that has progressed after CAR-T therapy. Participants must have measurable disease, be able to consent and follow the study plan, and meet certain blood count criteria. Those with more than one site of disease are eligible for the intervention arm.

Inclusion Criteria

Able and willing to provide written informed consent and to comply with the study protocol

I have a tumor that can be measured by scans.

Intervention arm: Platelet count ≥ 50 x 10^9/L at screening

Exclusion Criteria

Life expectancy < 30 days at the time of enrollment

History of prior allogeneic transplant or organ transplant

I have not had major surgery in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Safety Run-in

Evaluation of the tolerability and safety of tislelizumab or zanubrutinib monotherapy

6 weeks

2 cycles of monotherapy

Expanded Cohort

Combination therapy with tislelizumab and zanubrutinib for patients with acceptable toxicity profile and no disease progression

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tislelizumab
• Zanubrutinib

Trial Overview The study tests Zanubrutinib alone or combined with Tislelizumab in patients whose lymphoma worsened post-CAR-T treatment. It's a phase II trial aiming to assess how effective these drugs are in this situation.

Participant Groups

Group I: Zanubrutinib Experimental Treatment 1 Intervention

Zanubrutinib 160 mg oral twice daily - initial safety run-in period

Group II: Tislelizumab + Zanubrutinib Experimental Treatment 1 Intervention

Tislelizumab 200mg intravenously day 1 of each cycle every 3 weeks * Zanubrutinib 160 mg oral twice daily starts day 1 of each cycle - expanded cohort

Group III: Tislelizumab Experimental Treatment 1 Intervention

Tislelizumab 200mg intravenously every 3 weeks - initial safety run-in period

Group IV: Standard of Care Active Control 1 Intervention

Patients will receive standard of care, which is up to the investigator's discretion. This may include, but not limited to, palliative chemotherapy, steroids and/or radiation as deemed appropriate.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+