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PD1-CD19-CART in Patients With r/r B-cell Lymphoma

Sponsor
Bioray Laboratories (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04213469
Collaborator
First Affiliated Hospital of Zhejiang University (Other)
20
Enrollment
1
Location
1
Arm
36.6
Anticipated Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open label, single-site, dose-escalation study in up to 20 participants with relapse/refractory B-NHL. This study aims to evaluate the safety and efficacy of the treatment with PD1-CD19-CART.

Condition or Disease Intervention/Treatment Phase
  • Biological: PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
 N/A

Detailed Description

PD1-CD19-CART is a kind of chimeric antigen T cell targeting CD19 with both CD19-CAR gene integration and also PD1 knockout by one-step gene-editing. After completion of study treatment, subject participation for this study will be followed up to 15 years post T cell infusion.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
Patients will receive one of the three doses of 2*10^6/kg, 4*10^6/kg,6*10^6/kg.Patients will receive one of the three doses of 210^6/kg, 4106/kg,6*106/kg.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
a Safety and Efficacy Evaluation of PD1-CD19-CART in Patients With Relapse/Refractory B-cell Lymphoma
Actual Study Start Date :
Mar 13, 2020
Actual Primary Completion Date :
Nov 1, 2021
Anticipated Study Completion Date :
Apr 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: PD1-CD19-CART

Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine 4-6 days before CART infusion. A dose of PD1-CD19-CART will be infused on day 0.

Biological: PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1
Other Names:
  • PD1-CD19-CART

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose-limiting toxicity (DLT) [up to 28 days after T cell infusion]

      Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    Secondary Outcome Measures

    1. Objective response rate (ORR) [Baseline up to 3 months after T cell infusion]

      Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed.

    2. Progress free survival (PFS) [3 months]

      Assessed using modified Lugano classification response criteria for lymphoma (2014)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Have the capacity to give informed consent;

    2. ALL patients with the age between 18 and 65;

    3. Expected survival >3 moths;

    4. With no severe heart and lung disease;

    5. Previously confirmed diagnosis as CD19+ B-ALL or NHL within 6 months;

    6. Hematological index as following, white blood cell (WBC)≥1.5×109/L，absolute neutrophil count (ANC) ≥0.8×109/L, Platelet count≥50×109/L, Hemoglobin (Hgb) ≥ 90mg/L, lymphocyte count≥ 0.4×10^9/L；

    7. Blood biochemical index as no more than 1.5* ULN, including total bilirubin (TBIL), transglutaminase (AST), alanine aminotransferase (AST), Creatinine (SCr), Urea in patients with no tumor metastasis in liver and kidney; Blood biochemical index no more than 5* ULN in patients with tumor metastasis in liver and kidney;

    8. With a stable cardiac function, the left ventricular ejection fraction (LVEF) ≥ 55%;

    9. Virological tests were negative for EBV, CMV, HIV, TP and HCV; a negative HBV DNA test is acceptable if HBsAg is positive;

    10. ECOG <2;

    11. Relapsed or refractory (r/r) NHL including, Diffuse large B cell lymphoma(DLBCL, NOS), stage Ⅲ-Ⅳ;Primary mediastinal large B-cell lymphoma (PMBL), stage Ⅲ-Ⅳ; High grade B-cell lymphoma (HGBL), stage Ⅲ-Ⅳ; Mantle cell lymphoma (MCL), stage Ⅲ-Ⅳ; follicular lymphoma (FL), stage Ⅲ-Ⅳ and with aggression. r/r NHL defined as following, demonstrate disease that persists or relapse after achieving complete response (CR) after > 2 cycles of standard chemotherapy, or relapse after autologous hematopoietic stem cell transplantation (auto-HSCT), or not achieving CR after auto-HSCT.

    Exclusion Criteria:

    1. Pregnant or lactating women;

    2. With a pregnancy plan in the next 2 years;

    3. Prior treatment of anti-GVHD therapy;

    4. Acceptance of allogeneic stem cell transplant (ASCT);

    5. Isolated extramedullary relapse of ALL;

    6. Severe mental disorders, active autoimmune diseases, active infectious diseases, severe cardiovascular diseases;

    7. Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment;

    8. History of other type of maligant tumors;

    9. Any circumstances that possibly increase the risk of subjects or interfere with study results, which judged by investigator.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou Zhejiang China 310003

    Sponsors and Collaborators

    • Bioray Laboratories
    • First Affiliated Hospital of Zhejiang University

    Investigators

    • Principal Investigator: He Huang, Prof, the First Affliated Hospital, Zhejiang University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bioray Laboratories
    ClinicalTrials.gov Identifier:
    NCT04213469
    Other Study ID Numbers:
    • 2019-CAR-00CH2
    First Posted:
    Dec 30, 2019
    Last Update Posted:
    May 17, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, B-Cell

    Study Results

    No Results Posted as of May 17, 2022