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

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join if…

• Age ≥ 18 years
• Able and willing to provide written informed consent and to comply with the study protocol
• Radiologically measurable disease (≥ 1 nodal lesion > 2.0 cm in the longest diameter, and/or extranodal lesion > 1.0cm in the longest diameter)
• Intervention arm: Radiological measurable disease per inclusion criterion #3 with more than one site of disease.
• Relapse or refractory Large B cell Lymphoma post-CD19 directed CAR-T cell therapy within 6 weeks prior to enrollment (histological confirmation highly recommended although not mandatory)
• Intervention arm: Hemoglobin ≥ 80 g/L at screening*
• Intervention arm: Platelet count ≥ 75 x 109/L at screening*
• Intervention arm: Neutrophil count ≥ 1.0 x 109/L at screening*
• Intervention arm: ECOG performance status ≤ 2 at screening
• AST and ALT < 2.5 x ULN at screening
• Serum total bilirubin < 1.5 x ULN, except in patients with documented Gilberts syndrome at screening
• Creatinine clearance ≥ 30 mL/min as estimated by Cockcroft-gault equation at screening * Counts can be supported with growth factors or transfusions as per standard transfusion protocols.

🚫 You may not be able to join if…

• Life expectancy < 30 days at the time of enrollment
• Prior exposure to BTK or PD-1 inhibitor at any time prior to enrollment
• Prior anaphylactic reaction to monoclonal antibody therapy at any time prior to enrollment
• Intervention arm: On higher than physiologic doses (10mg daily) of prednisone daily at least 7 days prior to initiation of trial treatment. SOC arm: On prednisone for symptom management only.
• Uncontrolled autoimmune disease
• Known active CNS involvement disease
• History of prior allogeneic transplant or organ transplant
• Active bleeding or history of bleeding diathesis including, but not limited to,
  • History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
  • History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
• Difficulty with or unable to swallow oral medication, or known conditions that would significantly affect gastrointestinal function that would limit absorption of oral medication
• History of chronic or active, uncontrolled bacterial, viral or fungal infection; human T-cell lymphotropic virus type 1 seropositive status.
• Serologic status reflecting active viral hepatitis B or C infection as follows:
  • presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20IU), and if they are willing to be on appropriate prophylaxis and undergo monitoring for HBV reactivation if clinically indicated.
  • Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
• Individuals with known active HIV infection are eligible if CD4 and viral titres are controlled
• Any serious intercurrent illness, life threatening condition, organ system dysfunction including:
  • (1) Clinically significant cardiovascular including:
  • prolonged QTc > 480ms,
  • history of Mobitz II second degree or third degree heart block without a permanent pacemaker in situ,
  • uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure reading on 2 separate occasions showing systolic BP > 170 mmHg and/or diastolic BP > 105mmHg at screening,
  • uncontrolled or history of symptomatic arrhythmias (ie. sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes),
  • congestive heart failure or NYHA class ≥ 3,
  • myocardial infarction within 6 months prior to enrollment;
  • (2) History of significant cerebrovascular events including stroke or intracranial hemorrhage within 6 months prior to enrollment
• History of other active malignancies within 2 years prior to enrollment, with the exception of adequately treated in-situ carcinoma of cervix; localized basal cell or squamous cell carcinoma of skin; or previous malignancy confined and treated locally (surgery or other modality) with curative intent.
• Female patients of childbearing potential must practice highly effective methods (Section 6.7.1.1) of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥ 120 days after the last dose of zanubrutinib or tislelizumab
• Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with highly effective methods during the study treatment period and for ≥ 120 days after the last dose of zanubrutinib or tislelizumab.
• Major surgery within 4 weeks of the first dose of study drug
• Vaccination with a live vaccine within 28 days prior to the first dose of study drug
• Patient requires treatment with warfarin or other vitamin K antagonists
• Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, congestive obstructive pulmonary disease).

+ 11 more criteria — see the full checklist in the app.

Where this trial is running

• University Health Network (UHN), Toronto, Ontario, Canada

Who to contact

John Kuruvilla, FRCPC · 4169462821 · LymphomaClinicalTrials@uhn.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06167785.