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

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

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

Study Overview

• Status: Unknown
• Conditions: Diffuse Large B-cell Lymphoma; Rituximab; Toripalimab
• Intervention / Treatment: Drug: Toripalimab combine with Rituximab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Qin, doctor; Phone Number: 13601282738; Email: qinyan66@vip.sina.com

Study Locations

• China
  • Beijing, China
    • Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
    • Contact: Yan Qin, doctor; Phone Number: 13601282738; Email: qinyan66@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years old;
2. 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;
3. 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;
4. 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;
5. Recurrence confirmed by pathological biopsy and CD20 positive;
6. ECOG score 0-2 points;
7. No autoimmune diseases;

8. 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;

9. 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;
10. Patients must agree to take effective contraceptive measures during the study according to the investigator's request;
11. Understand and voluntarily sign written informed consent.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Toripalimab combine with Rituximab; 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.

Drug: Toripalimab combine with Rituximab; 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). Drug: Rituximab Rituximab is an antibody to CD20 molecules. One of the mechanisms of killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC).; Other Names: JS001 combine with rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	up to 24 months
Progression Free Survival(PFS)	From the date into this study to disease progression or death	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assessment of the safety events	Number of subjects experiencing different-grade toxicity	up to 24 months
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.	up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of the correlation between the ammount of T cells and NK cells around tumor cells	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.	up to 24 months
Change in immune microenviroment at the time of initial diagnosis and relapse	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.	up to 24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 7, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: DLBCL; Rituximab; Toripalimab; CD20
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: NCC2244

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No