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

Shanghai Jiao Tong University

Status and phase

Unknown

Phase 2

Conditions

EBV-Positive DLBCL, Nos

Primary Mediastinal Large B Cell Lymphoma

Treatments

Drug: Zanubrutinib

Drug: Tislelizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04705129

RJ-PMBCL-1

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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