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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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
Diffuse Large B-cell Lymphoma Rituximab Toripalimab Drug: Toripalimab combine with Rituximab 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : June 15, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arm Intervention/treatment
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 Name: JS001 combine with rituxan




Primary Outcome Measures :
  1. 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

  2. Progression Free Survival(PFS) [ Time Frame: up to 24 months ]
    From the date into this study to disease progression or death


Secondary Outcome Measures :
  1. To assessment of the safety events [ Time Frame: up to 24 months ]
    Number of subjects experiencing different-grade toxicity

  2. 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.


Other Outcome Measures:
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04425824


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

Locations
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China
Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, China
Contact: Yan Qin, doctor    13601282738    qinyan66@vip.sina.com   
Sponsors and Collaborators
Chinese Academy of Medical Sciences
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Responsible Party: Shi Yuankai, chief physician, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT04425824    
Other Study ID Numbers: NCC2244
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shi Yuankai, Chinese Academy of Medical Sciences:
DLBCL
CD20
Toripalimab
Rituximab
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents