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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
Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

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

    First Posted
    July 16, 2019
    Last Updated
    December 9, 2019
    Sponsor
    Chinese Academy of Medical Sciences
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    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

    Learn more about this trial

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

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