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

• ClinicalTrials.gov Identifier: NCT04425824
• Recruitment Status: Not yet recruiting
• First Posted: June 11, 2020
• Last Update Posted: June 16, 2020
• Sponsor: Chinese Academy of Medical Sciences
• Information provided by (Responsible Party): Shi Yuankai, Chinese Academy of Medical Sciences

Tracking Information

• First Submitted Date: June 4, 2020
• First Posted Date: June 11, 2020
• Last Update Posted Date: June 16, 2020
• Estimated Study Start Date: June 15, 2020
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 7, 2020)

• Objective Response Rate(ORR) [ Time Frame: up to 24 months ]
  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) [ Time Frame: up to 24 months ]
  From the date into this study to disease progression or death

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 7, 2020)

• To assessment of the safety events [ Time Frame: up to 24 months ]
  Number of subjects experiencing different-grade toxicity
• Assessment of the correlation between tumor cell PD-L1 expression intensity and efficacy [ Time Frame: up to 24 months ]
  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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 7, 2020)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Diffuse Large B-cell Lymphoma
• Rituximab
• Toripalimab

Intervention

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 Name: JS001 combine with rituxan

Study Arms

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.

Intervention: Drug: Toripalimab combine with Rituximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: June 7, 2020): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Yan Qin, doctor; 13601282738; qinyan66@vip.sina.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04425824
• Other Study ID Numbers: NCC2244
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Shi Yuankai, Chinese Academy of Medical Sciences
• Study Sponsor: Chinese Academy of Medical Sciences
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Chinese Academy of Medical Sciences
• Verification Date: June 2020