Zanubrutinib Combined With Tislelizumab in the Treatment of r/r PMBCL and EBV+ DLBCL

NCT ID: NCT04705129

Last Updated: 2021-03-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2024-01-01

Brief Summary

The study is to investigate the safety and efficacy of Zanubrutinib combined with Tislelizumab in the treatment of relapsed/refractory primary mediastinal large B-cell lymphoma and Epstein-Barr Virus-positive diffuse large B-cell lymphoma.

Detailed Description

R-CHOP regimen is the first-line therapy in DLBCL which greatly improved the efficacy of diffuse large B-cell lymphoma (DLBCL) and achieved good long-term survival. However, among DLBCL patients treated with R-CHOP, EBV+ had a lower 5-year OS than EBV- patients (65% vs 82%). For primary mediastinal large B-cell lymphoma (PMBCL), although the initial treatment has a better prognosis than DLBCL, there are still 10% to 30% of PMBCL patients with primary refractory or relapsed disease, and the prognosis is poor.

Zanubrutinib combined with Tislelizumab has been proved efficient in relapsed or refractory NHLs, with ORR rate 37%, CR rate of 16.7%. This phase II, prospective, open-label, single-arm study will evaluate the efficacy and safety of Zanubrutinib combined with Tislelizumab in the treatment of relapsed/refractory primary mediastinal large B-cell lymphoma and Epstein-Barr Virus-positive diffuse large B-cell lymphoma.

Conditions

Primary Mediastinal Large B Cell Lymphoma; EBV-Positive DLBCL, Nos

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

zanubrutinib+Tislelizumab

Zanubrutinib 160mg Bid, D1-21, po；Tislelizumab 200mg, D1, ivgtt

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

160mg Bid, D1-21, po

Tislelizumab

Intervention Type: DRUG

200mg, D1, ivgtt

Interventions

Zanubrutinib

160mg Bid, D1-21, po

Intervention Type: DRUG

Tislelizumab

200mg, D1, ivgtt

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed diffuse large B-cell lymphoma, EBV positive and primary mediastinal large B-cell lymphoma
• Have received at least one prior standard therapy line including Rituximab and anthracyclines.
• Age≥18
• ECOG 0,1,2
• Imaging accessible lesions
• Life expectancy>3 months
• Informed consented

Exclusion Criteria

• Have received systemic or local treatment including chemotherapy within three weeks before enrollment
• Chronic or active infectious diseases that require systemic antibiotics, antifungals or antiviral therapy
• Lab at enrollment (Unless caused by lymphoma) : Neutrophile<1.0*10^9/L , Hemoglobin<80g/L, Platelet<50*10^9/L, ALT or AST >2*ULN,AKP or bilirubin >1.5*ULN Creatinine>1.5*ULN
• Other uncontrollable medical condition that may that may interfere the participation of the study Not able to comply to the protocol for mental or other unknown reasons
• HIV infection
• If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA, DNA positive patients cannot be enrolled
• Previously received BTK inhibitor or anti-PD-1/PD-L1 treatment
• History of active autoimmune disease or severe autoimmune disease
• Need to be given corticosteroids (dose equivalent to prednisone >20 mg/day) or other immunosuppressive agents within 14 days before the study drug administration
• A history of interstitial lung disease or non-infectious pneumonia, except for those caused by radiotherapy
• Need strong cytochrome P450 (CYP) 3A inhibitor or inducer drug treatment
• Received live vaccination within 28 days before the first dose of study drug
• Patients who can receive hematopoietic stem cell transplantation, and if the subject has received allogeneic stem cell transplantation within 6 months before the first administration of the study drug or has active graft-versus-host disease requiring continuous immunosuppressive therapy
• Have received any experimental drug within 28 days, or the toxicity of any previous chemotherapy has not been relieved to ≤ Grade 1
• History of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, unless recovered for at least 2 years
• Have a history of other active malignancies within 2 years before entering the study, excluding cervical cancer in situ, local basal cell or squamous cell skin cancer that has been cured by adequate treatment; or the previous malignant tumor is localized and has undergone local radical treatment Treatment (surgery or other forms)
• Pregnant or nursing period
• Men or women who are fertile but refuse to take appropriate contraceptive measures, unless they have been surgically sterilized

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

First Deputy Director, Hematology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weili Zhao, PhD, MD

Role: STUDY_CHAIR

Ruijin Hospital

Locations

Ruijin Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Weili Zhao, PhD, MD

Role: CONTACT

zwl_trial@163.com

+862164370045

Pengpeng Xu, PhD, MD

Role: CONTACT

pengpeng_xu@126.com

+862164370045

Facility Contacts

Weili Zhao

Role: primary

zwl_trial@163.com

+862164370045

Other Identifiers

RJ-PMBCL-1

Identifier Type: -

Identifier Source: org_study_id