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CD19 CAR-T Expressing IL7 and CCL19 Combined With PD1 mAb for Relapsed or Refractory Diffuse Large B Cell Lymphoma (CICPD)

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: NCT04381741
Recruitment Status : Recruiting
First Posted : May 11, 2020
Last Update Posted : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary:
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for 35% of lymphoma. Chimeric antigen receptor T cell (CAR-T) therapy is a new method to treat DLBCL. KTE-C19, published in the New England Medical Journal in December 2017, was used to treat relapsed and refractory B-cell lymphoma. One year of treatment for 111 patients, the total response rate was 82%, and the complete remission rate was 54%. However, a large number of clinical studies have shown that about 20% of patients with B-ALL and 50% of patients with B-NHL cannot achieve complete remission (CR) after CD19-CAR-T treatment. Targeting tumor microenvironment is an important new method to overcome the drug resistance of CAR-T cells. In this study, IL-7 and CCL19 were connected on the basis of traditional second generation CD19 CAR-T cells to construct novel fourth generation CAR-T cells, which can promote the infiltration, accumulation and survival of CAR-T cells in lymphoma tissue, and further enhance the anti-tumor effect of traditional CAR-T cells. At the same time, combined with four generations of CAR-T cells and PD1 monoclonal antibody, PD1 / PDL1 signal pathway was blocked, anti-tumor effect of CAR-T was improved, and immune response and long-term remission rate of DLBCL were improved.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Biological: CD19-7×19 CAR-T plus PD1 monoclonal antibody Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CD19 CAR-T Expressing IL7 and CCL19 Combined With PD1 mAb for Relapsed or Refractory Diffuse Large B Cell Lymphoma
Actual Study Start Date : June 18, 2020
Estimated Primary Completion Date : September 1, 2023
Estimated Study Completion Date : September 1, 2023


Arm Intervention/treatment
Experimental: CD19-7×19 CAR-T plus PD1 monoclonal antibody Biological: CD19-7×19 CAR-T plus PD1 monoclonal antibody
Three different doses of CD19-7×19 CAR-T (1×106/kg、2×106/kg、3×106/kg) plus 200mg Tislelizumab every 3 weeks for 6 times




Primary Outcome Measures :
  1. Objective response rate [ Time Frame: 3 months ]
    Objective response rate of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb


Secondary Outcome Measures :
  1. progression-free survival [ Time Frame: 2 years ]
    progression-free survival of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb

  2. overall survival [ Time Frame: 2 years ]
    overall survival of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb

  3. Duration of Overall Response [ Time Frame: 2 years ]
    Duration of Overall Response of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb

  4. Relapse rate [ Time Frame: 2 years ]
    Relapse rate of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb



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 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • (1) Age ≥ 18, upper limit 75, unlimited for men and women;

    (2) ECOG score 0-3;

    (3) Histologically confirmed diffuse large B-cell lymphoma (DLBCL) [according to who 2008];

    (4) CD19 was positive (immunohistochemistry or flow cytometry).

    (5) The definition of refractory or relapse of DLBCL is: no complete remission after 2-line treatment; disease progression in any treatment process, or disease stabilization time equal to or less than 6 months; or disease progression or relapse within 12 months after hematopoietic stem cell transplantation;

    (6) The previous treatment of diffuse large B cell lymphoma must include rituximab (CD20 mAb) and anthracycline;

    (7) There should be at least one measurable focus. It is required that any length of lymph node focus should be greater than 1.5cm or any length of extranodal focus should be greater than 1.0cm. PET-CT scan focuses should have uptake (SUV is greater than liver blood pool);

    (8) The absolute value of neutrophils in peripheral blood ≥ 1000 / μ L, platelet ≥ 45000 / μ L;

    (9) Heart, liver and kidney function: creatinine < 1.5mg/dl; ALT (alanine aminotransferase) / AST (aspartate aminotransferase) 2.5 times lower than the normal upper limit; total bilirubin < 1.5mg/dl; heart ejection fraction (EF) ≥ 50%;

    (10) Sufficient understanding ability and voluntary signing of informed consent;

    (11) Those with fertility must be willing to use contraceptive methods;

    (12) According to the judgment of the researchers, the expected survival time is more than 4 months;

    (13) Willing to follow visit schedule, administration plan, laboratory inspection and other test steps.

Exclusion Criteria:

  • (1) History of other tumors;

    (2) Hematopoietic stem cell transplantation was performed within 6 weeks;

    (3) Any target car-t treatment was performed within 3 months before the car-t treatment;

    (4) Previous use of any commercially available PD-1 mAb;

    (5) Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection;

    (6) Active autoimmune diseases;

    (7) Uncontrollable infection of active bacteria and fungi;

    (8) HIV infection, syphilis infection; active hepatitis B or C: hepatitis B: HBV-DNA ≥ 1000IU / ml; hepatitis C: HCV RNA positive and liver function abnormal.

    (9) Known central nervous system lymphoma.


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): NCT04381741


Contacts
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Contact: Hui Liu, MD, PhD +8613819198629 sylenliu@163.com
Contact: Wenbin Qian, MD, PhD +8613605801032 qianwb@zju.edu.cn

Locations
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China, Zhejiang
2nd Affiliated Hospital, School of Medicine, Zhejiang University Recruiting
Hangzhou, Zhejiang, China, 310009
Contact: Hui Liu, MD, PhD    +8613819198629    sylenliu@163.com   
Contact: Wenbin Qian, MD, PhD    +8613605801032    qianwb@zju.edu.cn   
Sponsors and Collaborators
Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
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Principal Investigator: Wenbin Qian, MD, PhD 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
  Study Documents (Full-Text)

Documents provided by Second Affiliated Hospital, School of Medicine, Zhejiang University:
Informed Consent Form  [PDF] March 20, 2020

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Responsible Party: Second Affiliated Hospital, School of Medicine, Zhejiang University
ClinicalTrials.gov Identifier: NCT04381741    
Other Study ID Numbers: IR2020001132
First Posted: May 11, 2020    Key Record Dates
Last Update Posted: June 29, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Second Affiliated Hospital, School of Medicine, Zhejiang University:
diffuse large B-cell lymphoma
Chimeric antigen receptor T cell
PD1 monoclonal antibody
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
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs