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

NCT ID: NCT04023916

Last Updated: 2019-12-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-01
• Study Completion Date: 2021-07-30

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.

Conditions

Diffuse Large B-Cell Lymphoma; Sintilimab; TP53 Mutation

Keywords

DLBCL; Sintilimab; R-CHOP; TP53; PD-L1

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

Sintilimab-R-CHOP

Intervention Type: DRUG

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.

Interventions

Sintilimab-R-CHOP

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.

Intervention Type: DRUG

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Shi Yuankai

vice president

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuankai Shi, M.D

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Central Contacts

Yuankai Shi, M.D

Role: CONTACT

Phone: 86 010-87788293

Email: syuankaipumc@126.com

Yan Qin, M.D

Role: CONTACT

Phone: 86 010-87788293

Email: 13601282738@163.com

Other Identifiers

NCC2066

Identifier Type: -

Identifier Source: org_study_id