Sintilimab Plus R-CHOP as the First-line Treatment in Patients With Diffuse Large B-Cell Lymphoma.

Phase 2

• Conditions: TP53 Mutation; Diffuse Large B-Cell Lymphoma; Sintilimab
• Interventions: Drug: Sintilimab-R-CHOP

• Registration Number: NCT04023916
• Lead Sponsor: Chinese Academy of Medical Sciences

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.

Study Timeline

• Study First Submitted: 2019-07-16
• Study First Submitted QC: 2019-07-16
• Study First Posted: 2019-07-18
• Status Verified: 2019-12
• Study Start: 2019-12-01
• Last Update Submitted: 2019-12-09
• Last Update Posted: 2019-12-11
• Primary Completion: 2020-07-30
• Study Completion: 2021-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Diagnosed as diffuse large B-cell Lymphoma with positive CD20 results;
2. Age between 18 to 70 years old;
3. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2;
4. No history of malignant tumors, having no tumor other than DLBCL at the time of enrollment;
5. Life expectancy no less than 6 months;
6. The patient or his/her attorney would be able to provide written consent for necessary examinations or procedures;
7. Ann Arbor stage I~ IV
8. previously untreated advanced DLBCL.
9. At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
10. Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of DLBCL.
11. Agree to remain abstinent or use contraceptive measures.

Exclusion Criteria

1. History of autologous stem cell transplantation,radiotherapy or chemotherapy.
2. History of other malignant tumors, except skin basal cell carcinoma and in situ cervical cancer;
3. With uncontrolled cardiovascular/ cerebrovascular disease, coagulation disorders, connective tissue disease, severe infectious diseases;
4. Lymphoma originated in the central nervous system;
5. Left ventricular ejection fraction ≦50％;
6. 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;
7. Other uncontrolled medical conditions which the investigators think might influence the results of the trial;
8. Patients with mental illnesses or other diseases that might not comply with the trial plan;
9. Women during pregnancy or lactation;
10. HIV positive patients;
11. 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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sintilimab-R-CHOP	Sintilimab-R-CHOP	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.

Primary Outcome Measures

Name	Time	Method
complete remission rate	every 3 months until 30 months after the last patient's enrollment.	complete remission rate after treated by Sintilimab+ R-CHOP regimen.

Secondary Outcome Measures

Name	Time	Method
overall survival	30 months after the last patient's enrollment	from the date of inclusion to date of death, irrespective of cause
adverse events	from the date of first cycle of treatment to 30 months after last patient's enrollment	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.