NCT06167785

A Study to Evaluate Zanubrutinib and Tislelizumab in Progressive Lymphoma Post CAR-T

A Prospective, Multicenter, Phase II Trial to Evaluate the Efficacy of Zanubrutinib and Tislelizumab as Well as Standard of Care for the Treatment of Patients With Progressive Lymphoma Post Anti-CD19 CAR-T Cell Therapy

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Sponsor: University Health Network, Toronto · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Given that this group of patients is a heavily pre-treated group of individuals, the study will be broken into 2 distinct parts; an initial safety run-in period and an expanded cohort. During both distinct parts of the study, patients meeting all the eligibility criteria except for the criteria specific to enrollment in the intervention arm, can be enrolled into the standard of care (SOC) arm. Initial safety run-in period: intervention arm: The initial safety run-in period will evaluate the tolerability and safety of tislelizumab or zanubrutinib monotherapy. In this initial phase, a total of 10 patients (5/ arm) will receive either zanubrutinib or tislelizumab monotherapy). Once the 10th patient has received 2 cycles of monotherapy, an early safety interim analysis will be complete to ensure the safety and tolerability of individual agents. These patients can continue to receive monotherapy until the results of the early safety interim analysis are known, at which point, if the study will move into the expanded cohort phase, these patients are eligible to receive the combination therapy. Enrollment into the intervention arm will be paused after the enrollment of the 10th patient in the initial safety run-in period intervention arm, until it is determined the study will move into the expanded cohort phase. Enrollment of patients into the SOC arm can continue during this time. Expanded cohort: intervention arm: If monotherapy with tislelizumab and zanubrutinib are determined to be safe following the early safety interim analysis, then combination therapy will be explored in the expanded cohort. Patients will receive tislelizumab in combination with oral zanubrutinib. Patients that initially received monotherapy with tislelizumab or zanubrutinib, as part of the safety run in, will have the other drug added in for the remaining cycles. Patients will be allowed to continue in the study as long as they have acceptable toxicity profile and do not show disease progression, for up to a total of 34 cycles (\~ 2 years) of treatment.

Conditions

• Large B-cell Lymphoma

Interventions

Type	Name	Description
DRUG	Tislelizumab	Tislelizumab 200mg intravenously every 3 weeks
DRUG	Zanubrutinib	Zanubrutinib 160 mg oral twice daily
DRUG	Tislelizumab + Zanubrutinib	Tislelizumab 200mg intravenously day 1 of each cycle every 3 weeks + Zanubrutinib 160 mg oral twice daily starts day 1 of each cycle

Timeline

• Start date: 2025-06-04
• Primary completion: 2026-04-01
• Completion: 2027-12-01
• First posted: 2023-12-13
• Last updated: 2025-06-19

Locations

1 site across 1 country: Canada