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

Diffuse Large B-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04425824
• Other study ID #: NCC2244
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 15, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2020
• Source: Chinese Academy of Medical Sciences
• Contact: Yan Qin, doctor
• Phone: 13601282738
• Email: qinyan66[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• 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).

Locations

Country	Name	City	State
China	Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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,ß2-MG,CIITA,HLA-DR/DP/DQ positive cells.	up to 24 months
Primary	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
Primary	Progression Free Survival(PFS)	From the date into this study to disease progression or death	up to 24 months
Secondary	To assessment of the safety events	Number of subjects experiencing different-grade toxicity	up to 24 months
Secondary	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