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Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma

Primary Purpose

Diffuse Large B-cell Lymphoma, Rituximab, Toripalimab

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Toripalimab combine with Rituximab

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring DLBCL, CD20, Toripalimab, Rituximab

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥18 years old;
According to the WHO 2016 classification criteria, the CD20 positive diffuse large B-cell lymphoma (DLBCL) diagnosed by pathology should include the indicators of immunohistochemistry: CD10, BCL-2, MUM-1, BCL-6 and C-MYC;
Relapsed or refractory DLBCL.Patients younger than 65 years should relapse or progress after receiving at least second-line treatment, and patients 65 years of age and older could be intolerant to second-line treatment, and they who relapse or progress after receiving first-line treatment;
There is at least one measurable lesion, defined as measurable dual-diameter, intra-lymph node lesion, short diameter> 1.5cm, extra-lymph node lesion short diameter> 1.0cm;
Recurrence confirmed by pathological biopsy and CD20 positive;
ECOG score 0-2 points;
No autoimmune diseases;
Blood routine examination meets the following criteria:
1. Neutrophil count ≥ 1.5 x 109 / L,;
2. Platelet ≥ 75 x 109 / L,;
3. Hemoglobin ≥ 10.0 g / dL;
The main organ function meets the following criteria:
1. Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper limit of normal value;
2. Bilirubin ≤ 2.0 mg / dL;
3. Creatinine clearance rate ≥ 60 mL / min;
Patients must agree to take effective contraceptive measures during the study according to the investigator's request;
Understand and voluntarily sign written informed consent.

Exclusion Criteria:

Diagnosed as transformed diffuse large B-cell lymphoma;
Diagnosed as double-hit diffuse large B-cell lymphoma (DHL);
Diagnosed as primary or secondary central nervous system lymphoma;
HBV DNA positive or HCV RNA positive patients;
Left ventricular ejection fraction <50%;
Patients with history of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis
Patients are using or have been used immunosuppressive drugs
Patients with ≥2 grade peripheral neuropathy

Sites / Locations

Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Toripalimab combine with Rituximab

Arm Description

Experimental: Toripalimab combine with Rituximab Induction period: Toripalimab 240mg administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles. Rituximab 375mg/m² administered intravenously (IV) on Day 1 of each 21-day cycle for 6 cycles. Maintenance: Toripalimab 240mg administered intravenously (IV) and Rituximab 375mg/m² on Day 1 of each 56-day cycle for 6 cycles.

Outcomes

Primary Outcome Measures

Objective Response Rate(ORR)

From the beginning of treatment, adopt Lugano 2014 evaluation standard, imaging examinations are performed every 2 cycles to assess changes in disease until progression or death

Progression Free Survival(PFS)

From the date into this study to disease progression or death

Secondary Outcome Measures

To assessment of the safety events

Number of subjects experiencing different-grade toxicity

Assessment of the correlation between tumor cell PD-L1 expression intensity and efficacy

Subjects will be according to the Lugano 2014 criteria assessed with computed tomograph(CT) at screening,after completion of treantment therapy and during the post-treatment follow-up period.Baseline biopsies for immunologic analyses will be obtained from patients. Secondary histologic outcome include percent PD-L1 positive tumor cells by immunohistochemistry.

Full Information

NCT ID

NCT04425824

First Posted

June 4, 2020

Last Updated

June 12, 2020

Sponsor

Chinese Academy of Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT04425824

Brief Title

Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma

Official Title

Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma: An Exploratory Small Sample, Phase II, Single-center Clinical Trail

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Unknown status

Study Start Date

June 15, 2020 (Anticipated)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

December 31, 2022 (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

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Exploring the efficacy and safety of Toripalimab with Rituximab for treatment of relapsed refractory CD20 positive diffuse large B-cell lymphoma.

Detailed Description

Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2). Rituximab is an antibody to CD20 molecules. One of the mechanisms of killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC). These two drugs may have a synergistic effect on anti-tumor. The purpose of this study is to determine whether Toripalimab with Rituximab is effective and safe for treatment of relapsed refractory CD20 positive diffuse large B-cell lymphoma. This is an exploratory small sample, phase II, single-center clinical trial, which is going to enroll 20 participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B-cell Lymphoma, Rituximab, Toripalimab

Keywords

DLBCL, CD20, Toripalimab, Rituximab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Toripalimab combine with Rituximab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Toripalimab combine with Rituximab

Other Intervention Name(s)

JS001 combine with rituxan

Intervention Description

Primary Outcome Measure Information:

Title

Objective Response Rate(ORR)

Description

From the beginning of treatment, adopt Lugano 2014 evaluation standard, imaging examinations are performed every 2 cycles to assess changes in disease until progression or death

Time Frame

up to 24 months

Title

Progression Free Survival(PFS)

Description

From the date into this study to disease progression or death

Time Frame

up to 24 months

Secondary Outcome Measure Information:

Title

To assessment of the safety events

Description

Number of subjects experiencing different-grade toxicity

Time Frame

up to 24 months

Title

Assessment of the correlation between tumor cell PD-L1 expression intensity and efficacy

Description

Time Frame

up to 24 months

Other Pre-specified Outcome Measures:

Title

Analysis of the correlation between the ammount of T cells and NK cells around tumor cells

Description

Baseline and post-treatment biopsies for immunologic analyses will be obtained from patients.Histologic outcomes include percent and density PD-L1 positive tumor cells, percent and density CD56 postive NK cells, percent and density CD3 positive T cells by immunohistochemistry.

Time Frame

up to 24 months

Title

Change in immune microenviroment at the time of initial diagnosis and relapse

Description

Immune mincroenviroment to be assessed by analyzing changes in the immune infiltrate in biopsy specimens obtained at initial diagnosis and relapse. Histologic outcome include percent and density PD-L1 positive tumor cells and CD3,CD4,CD8,CD56,CD58,PD-1,β2-MG,CIITA,HLA-DR/DP/DQ positive cells.

Time Frame

up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥18 years old; According to the WHO 2016 classification criteria, the CD20 positive diffuse large B-cell lymphoma (DLBCL) diagnosed by pathology should include the indicators of immunohistochemistry: CD10, BCL-2, MUM-1, BCL-6 and C-MYC; Relapsed or refractory DLBCL.Patients younger than 65 years should relapse or progress after receiving at least second-line treatment, and patients 65 years of age and older could be intolerant to second-line treatment, and they who relapse or progress after receiving first-line treatment; There is at least one measurable lesion, defined as measurable dual-diameter, intra-lymph node lesion, short diameter> 1.5cm, extra-lymph node lesion short diameter> 1.0cm; Recurrence confirmed by pathological biopsy and CD20 positive; ECOG score 0-2 points; No autoimmune diseases; Blood routine examination meets the following criteria: Neutrophil count ≥ 1.5 x 109 / L,; Platelet ≥ 75 x 109 / L,; Hemoglobin ≥ 10.0 g / dL; The main organ function meets the following criteria: Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper limit of normal value; Bilirubin ≤ 2.0 mg / dL; Creatinine clearance rate ≥ 60 mL / min; Patients must agree to take effective contraceptive measures during the study according to the investigator's request; Understand and voluntarily sign written informed consent. Exclusion Criteria: Diagnosed as transformed diffuse large B-cell lymphoma; Diagnosed as double-hit diffuse large B-cell lymphoma (DHL); Diagnosed as primary or secondary central nervous system lymphoma; HBV DNA positive or HCV RNA positive patients; Left ventricular ejection fraction <50%; Patients with history of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis Patients are using or have been used immunosuppressive drugs Patients with ≥2 grade peripheral neuropathy

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yan Qin, doctor

Phone

13601282738

qinyan66@vip.sina.com

Facility Information:

Facility Name

Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

City

Beijing

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yan Qin, doctor

Phone

13601282738

qinyan66@vip.sina.com

12. IPD Sharing Statement

Learn more about this trial

Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma

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