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

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

Tracking Information
First Submitted Date  ICMJE June 4, 2020
First Posted Date  ICMJE June 11, 2020
Last Update Posted Date June 16, 2020
Estimated Study Start Date  ICMJE June 15, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE 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  ICMJE Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diffuse Large B-cell Lymphoma
  • Rituximab
  • Toripalimab
Intervention  ICMJE 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  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 7, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yan Qin, doctor 13601282738 qinyan66@vip.sina.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04425824
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Shi Yuankai, Chinese Academy of Medical Sciences
Study Sponsor  ICMJE Chinese Academy of Medical Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chinese Academy of Medical Sciences
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP