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

Phase 2

• Conditions: Rituximab; Diffuse Large B-cell Lymphoma; Toripalimab
• Interventions: Drug: Toripalimab combine with Rituximab

• Registration Number: NCT04425824
• Lead Sponsor: Chinese Academy of Medical Sciences

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 Timeline

• Status Verified: 2020-06
• Study First Submitted: 2020-06-04
• Study First Submitted QC: 2020-06-07
• Study First Posted: 2020-06-11
• Last Update Submitted: 2020-06-12
• Study Start: 2020-06-15
• Last Update Posted: 2020-06-16
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Toripalimab combine with Rituximab	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate(ORR)	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)	up to 24 months	From the date into this study to disease progression or death

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; 🇨🇳 Beijing, China