Back to resultsZanubrutinib Combined With Tislelizumab in the Treatment of r/r PMBCL and EBV+ DLBCL
Primary Purpose
Primary Mediastinal Large B Cell Lymphoma, EBV-Positive DLBCL, Nos
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib
Tislelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Primary Mediastinal Large B Cell Lymphoma focused on measuring Primary Mediastinal Large B Cell Lymphoma, EBV-Positive DLBCL, nos, targeted therapy
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
Sites / Locations
- Ruijin HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
zanubrutinib+Tislelizumab
Arm Description
Zanubrutinib 160mg Bid, D1-21, po；Tislelizumab 200mg, D1, ivgtt
Outcomes
Primary Outcome Measures
complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria
Secondary Outcome Measures
progression free survival
Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.
overall survival
Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04705129
Brief Title
Zanubrutinib Combined With Tislelizumab in the Treatment of r/r PMBCL and EBV+ DLBCL
Official Title
A Phase II Study on 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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
January 1, 2023 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Mediastinal Large B Cell Lymphoma, EBV-Positive DLBCL, Nos
Keywords
Primary Mediastinal Large B Cell Lymphoma, EBV-Positive DLBCL, nos, targeted therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
zanubrutinib+Tislelizumab
Arm Type
Experimental
Arm Description
Zanubrutinib 160mg Bid, D1-21, po；Tislelizumab 200mg, D1, ivgtt
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Intervention Description
160mg Bid, D1-21, po
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
200mg, D1, ivgtt
Primary Outcome Measure Information:
Title
complete response rate
Description
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria
Time Frame
21 days after 6 cycles of treatment (each cycle is 21 days)
Secondary Outcome Measure Information:
Title
progression free survival
Description
Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.
Time Frame
2 year
Title
overall survival
Description
Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.
Time Frame
2 year
Title
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events
Time Frame
Up to 30 days after completion of study treatment
Other Pre-specified Outcome Measures:
Title
The significance of biomarkers in tissue and plasma including cfDNA, PD-1,PD-L1
Description
Dynamic change of the expression of PD-1, PD-L1
Time Frame
through study completion，an average of 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weili Zhao, PhD, MD
Phone
+862164370045
Email
zwl_trial@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pengpeng Xu, PhD, MD
Phone
+862164370045
Email
pengpeng_xu@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weili Zhao, PhD, MD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili Zhao
Phone
+862164370045
Email
zwl_trial@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Zanubrutinib Combined With Tislelizumab in the Treatment of r/r PMBCL and EBV+ DLBCL
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