Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies

Sponsor
Wuhan Sian Medical Technology Co., Ltd (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04008251
Collaborator
Wuhan Union Hospital, China (Other), Jingzhou Central Hospital (Other), Xiangyang Central Hospital (Other), People Hospital Of Yichang (Other)
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Study Details

Study Description

Brief Summary

This is a single arm, open-label study to evaluate the safety and efficacy of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.

Condition or Disease Intervention/Treatment Phase
  • Genetic: Second generation humanized CAR-T cells
Phase 1

Detailed Description

Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CAR-T therapy showed great effect on patients with relapsed or refractory B cell malignancies. To improve the efficacy and safety, the researchers designed a second-generation humanized CAR, consisting of humanized CD19 single chain variable fragment (scFv) and CD137 costimulatory domain. This study aims to evaluate the safety and effectiveness of humanized anti-CD19 CAR-T cells in patients with relapsed or refractory B cell Malignancies.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Treatment of Relapsed or Refractory B-cell Malignancies by Humanized CD19 Chimeric Antigen Receptor (CAR)-Modified T Cells
Actual Study Start Date :
May 27, 2019
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Second generation humanized CAR-T cells

Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.

Genetic: Second generation humanized CAR-T cells
Patients receive humanized CD19 CAR-T cells transduced with a lentiviral vector on days 0/1/2 in the absence of disease progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

  1. Number of participants with adverse events [5 years]

    Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)

Secondary Outcome Measures

  1. One-month remission rate [1 month]

    Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).

  2. Overall survival [5 years]

    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).

  3. Event-free survival [5 years]

    EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).

  4. Relapse-free survival [5 years]

    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).

  5. Rate of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells [5 years]

    In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.

  6. Quantity of anti-CD19 CAR-T cells in bone marrow cells and peripheral blood cells [5 years]

    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.

  7. Quantity of anti-CD19 CAR copies in bone marrow cells and peripheral blood cells [5 years]

    In vivo (bone marrow and peripheral blood) quantity of anti-CD19 CAR copies were determined by means of qPCR.

Eligibility Criteria

Criteria

Ages Eligible for Study:
14 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy; or relapsed after auto-HSCT/allo-HSCT; or patients voluntarily choose CD19 CAR-T cells as a first treatment;

  2. B cell hematological malignancies include the following three categories:

  1. B-cell acute lymphocytic leukemia (B-ALL);

  2. Indolent B-cell lymphoma (CLL, FL, MZL, LPL);

  3. Aggressive B-cell lymphoma (DLBCL, BL, MCL);

  1. Aged from 14 to 70 years old;

  2. Expected survival time > 6 months;

  3. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;

  4. Voluntarily participate in this experiment and sign informed consent by themself, or legally authorized representative.

Exclusion Criteria:
  1. With a history of epilepsy or other central nervous system diseases;

  2. Having graft-versus-host reaction, requires the use of immunosuppressants;

  3. The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);

  4. Pregnant or lactating women (safety of this therapy for the unborn child is unknown);

  5. Not curable active infection;

  6. Patients with active hepatitis B or hepatitis C virus infection;

  7. Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);

  8. Using product of gene therapy before;

  9. Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);

  10. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;

  11. Patients with HIV-infection;

  12. Any situation that may increase the risk of patients or interfere with test results.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei China 430022

Sponsors and Collaborators

  • Wuhan Sian Medical Technology Co., Ltd
  • Wuhan Union Hospital, China
  • Jingzhou Central Hospital
  • Xiangyang Central Hospital
  • People Hospital Of Yichang

Investigators

  • Principal Investigator: Heng Mei, M.D., Ph.D, Wuhan Union Hospital, China

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Wuhan Sian Medical Technology Co., Ltd
ClinicalTrials.gov Identifier:
NCT04008251
Other Study ID Numbers:
  • CART-huCD19-01
First Posted:
Jul 5, 2019
Last Update Posted:
Aug 7, 2019
Last Verified:
Jul 1, 2019
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:

Study Results

No Results Posted as of Aug 7, 2019