Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
Other Outcome Measures
- Analysis of the correlation between the ammount of T cells and NK cells around tumor cells [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 [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years old;
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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;
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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;
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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;
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Recurrence confirmed by pathological biopsy and CD20 positive;
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ECOG score 0-2 points;
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No autoimmune diseases;
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Blood routine examination meets the following criteria:
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Neutrophil count ≥ 1.5 x 109 / L,;
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Platelet ≥ 75 x 109 / L,;
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Hemoglobin ≥ 10.0 g / dL;
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The main organ function meets the following criteria:
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Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper limit of normal value;
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Bilirubin ≤ 2.0 mg / dL;
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Creatinine clearance rate ≥ 60 mL / min;
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Patients must agree to take effective contraceptive measures during the study according to the investigator's request;
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Understand and voluntarily sign written informed consent.
Exclusion Criteria:
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Diagnosed as transformed diffuse large B-cell lymphoma;
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Diagnosed as double-hit diffuse large B-cell lymphoma (DHL);
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Diagnosed as primary or secondary central nervous system lymphoma;
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HBV DNA positive or HCV RNA positive patients;
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Left ventricular ejection fraction <50%;
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Patients with history of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis
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Patients are using or have been used immunosuppressive drugs
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Patients with ≥2 grade peripheral neuropathy
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College | Beijing | China |
Sponsors and Collaborators
- Chinese Academy of Medical Sciences
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCC2244