Sintilimab Plus R-CHOP as the First-line Treatment in Patients With Diffuse Large B-Cell Lymphoma.
Primary Purpose
Diffuse Large B-Cell Lymphoma, Sintilimab, TP53 Mutation
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sintilimab-R-CHOP
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring DLBCL, Sintilimab, R-CHOP, TP53, PD-L1
Eligibility Criteria
Inclusion Criteria:
- Diagnosed as diffuse large B-cell Lymphoma with positive CD20 results;
- Age between 18 to 70 years old;
- World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2;
- No history of malignant tumors, having no tumor other than DLBCL at the time of enrollment;
- Life expectancy no less than 6 months;
- The patient or his/her attorney would be able to provide written consent for necessary examinations or procedures;
- Ann Arbor stage I~ IV
- previously untreated advanced DLBCL.
- At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
- Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of DLBCL.
- Agree to remain abstinent or use contraceptive measures.
Exclusion Criteria:
- History of autologous stem cell transplantation,radiotherapy or chemotherapy.
- History of other malignant tumors, except skin basal cell carcinoma and in situ cervical cancer;
- With uncontrolled cardiovascular/ cerebrovascular disease, coagulation disorders, connective tissue disease, severe infectious diseases;
- Lymphoma originated in the central nervous system;
- Left ventricular ejection fraction ≦50%;
- Abnormal lab results in enrollment:Neutrophil count: <1.5*10^9/L;Platelet count <75*10^9/L;AST or ALT >2 times the upper limit of normal level,AKP and total bilirubin >1.5 times the upper limit of normal level;serum creatinine >1.5 times the upper limit of normal level;
- Other uncontrolled medical conditions which the investigators think might influence the results of the trial;
- Patients with mental illnesses or other diseases that might not comply with the trial plan;
- Women during pregnancy or lactation;
- HIV positive patients;
- HbsAg (+) patients with HBV DNA(+), can be enrolled only when his/her HBV DNA turns negative; patients with HBsAg(-) HBcAb(+) can be enrolled only when his/her HBV DNA turns negative;
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sintilimab-R-CHOP
Arm Description
Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and Sintilimab, rituximab, and CHOP during Cycles 2-6 (21-day cycle) ,Sintilimab and rituximab during Cycles 6-8 (21-day cycle) , followed by Sintilimab from Cycles 9-14 (8-week cycle) during consolidation treatment.
Outcomes
Primary Outcome Measures
complete remission rate
complete remission rate after treated by Sintilimab+ R-CHOP regimen.
Secondary Outcome Measures
overall survival
from the date of inclusion to date of death, irrespective of cause
adverse events
any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.For safety reasons, the initial enrollment of the first 6 patients in the study will be slow and conduct intensive monitoring for safety. the monitoring time window for each patient is 21 days after the first treatment. If the dose-limited toxicity event was observed in more than 2 of the first 6 patients and was assessed by the research team as caused by cumulative exposure to the study drug combination therapy, the trial will be stopped.
Full Information
NCT ID
NCT04023916
First Posted
July 16, 2019
Last Updated
December 9, 2019
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT04023916
Brief Title
Sintilimab Plus R-CHOP as the First-line Treatment in Patients With Diffuse Large B-Cell Lymphoma.
Official Title
Phase II Study of Sintilimab Plus R-CHOP as the First-line Treatment for DLBCL Patients With TP53 Mutation and PD-L1 Positive.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 1, 2019 (Anticipated)
Primary Completion Date
July 30, 2020 (Anticipated)
Study Completion Date
July 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Sintilimab and R-CHOP regimen as the first-line treatment for DLBCL patients with TP53 mutation and PD-L1 positive.
Detailed Description
This Phase II, open-label, single-center, non-randomized study will evaluate the safety and efficacy of induction treatment consisting of Sintilimab in combination with Rituximab plus chemotherapy (R-CHOP) as the first-line treatment in participants with DLBCL, followed by consolidation treatment with Sintilimab alone in patients who achieve CR at the end of induction.For safety reasons, the initial enrollment of the first 6 patients in the study will be slow and conduct intensive monitoring for safety. If the dose-limited toxicity event was observed in more than 2 of the first 6 patients and was assessed caused by cumulative exposure to the study drug combination therapy, the trial will be stopped.This study also aim to evaluate the correlation of clinical efficacy to the expression of PD-L1,PD-1,CD3,CD4,CD8,CD56,CD58,β2-MG,HLA-DR/DP/DQ and so on by immunohistochemical techniques.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma, Sintilimab, TP53 Mutation
Keywords
DLBCL, Sintilimab, R-CHOP, TP53, PD-L1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sintilimab-R-CHOP
Arm Type
Experimental
Arm Description
Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and Sintilimab, rituximab, and CHOP during Cycles 2-6 (21-day cycle) ,Sintilimab and rituximab during Cycles 6-8 (21-day cycle) , followed by Sintilimab from Cycles 9-14 (8-week cycle) during consolidation treatment.
Intervention Type
Drug
Intervention Name(s)
Sintilimab-R-CHOP
Intervention Description
Drug:Sintilimab:
Sintilimab:200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 200 mg IV on Day 1 of Cycles 9-14.
Drug: Rituximab Rituximab:Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m^2 IV on Day 1 of Cycle 1-8, during induction treatment.
Drug: Cyclophosphamide Cyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 2 of Cycle 1-6, during induction treatment.
Drug: Doxorubicin Hydrochloride Liposome Injection Doxorubicin Hydrochloride Liposome Injection will be administered at a dose of 35 mg/m^2 IV on Day 2-3 of Cycle 1-6, during induction treatment.
Drug: Vincristine Vincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 2 of Cycle 1-6, during induction treatment.
Drug: Prednisone Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6, during induction treatment. Prednisolone may be given if prednisone is unavailable.
Primary Outcome Measure Information:
Title
complete remission rate
Description
complete remission rate after treated by Sintilimab+ R-CHOP regimen.
Time Frame
every 3 months until 30 months after the last patient's enrollment.
Secondary Outcome Measure Information:
Title
overall survival
Description
from the date of inclusion to date of death, irrespective of cause
Time Frame
30 months after the last patient's enrollment
Title
adverse events
Description
any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.For safety reasons, the initial enrollment of the first 6 patients in the study will be slow and conduct intensive monitoring for safety. the monitoring time window for each patient is 21 days after the first treatment. If the dose-limited toxicity event was observed in more than 2 of the first 6 patients and was assessed by the research team as caused by cumulative exposure to the study drug combination therapy, the trial will be stopped.
Time Frame
from the date of first cycle of treatment to 30 months after last patient's enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed as diffuse large B-cell Lymphoma with positive CD20 results;
Age between 18 to 70 years old;
World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2;
No history of malignant tumors, having no tumor other than DLBCL at the time of enrollment;
Life expectancy no less than 6 months;
The patient or his/her attorney would be able to provide written consent for necessary examinations or procedures;
Ann Arbor stage I~ IV
previously untreated advanced DLBCL.
At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of DLBCL.
Agree to remain abstinent or use contraceptive measures.
Exclusion Criteria:
History of autologous stem cell transplantation,radiotherapy or chemotherapy.
History of other malignant tumors, except skin basal cell carcinoma and in situ cervical cancer;
With uncontrolled cardiovascular/ cerebrovascular disease, coagulation disorders, connective tissue disease, severe infectious diseases;
Lymphoma originated in the central nervous system;
Left ventricular ejection fraction ≦50%;
Abnormal lab results in enrollment:Neutrophil count: <1.5*10^9/L;Platelet count <75*10^9/L;AST or ALT >2 times the upper limit of normal level,AKP and total bilirubin >1.5 times the upper limit of normal level;serum creatinine >1.5 times the upper limit of normal level;
Other uncontrolled medical conditions which the investigators think might influence the results of the trial;
Patients with mental illnesses or other diseases that might not comply with the trial plan;
Women during pregnancy or lactation;
HIV positive patients;
HbsAg (+) patients with HBV DNA(+), can be enrolled only when his/her HBV DNA turns negative; patients with HBsAg(-) HBcAb(+) can be enrolled only when his/her HBV DNA turns negative;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuankai Shi, M.D
Phone
86 010-87788293
Email
syuankaipumc@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Qin, M.D
Phone
86 010-87788293
Email
13601282738@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuankai Shi, M.D
Organizational Affiliation
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Sintilimab Plus R-CHOP as the First-line Treatment in Patients With Diffuse Large B-Cell Lymphoma.
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