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A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies

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ClinicalTrials.gov Identifier: NCT03050190
Recruitment Status : Unknown
Verified September 2019 by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute.
Recruitment status was:  Recruiting
First Posted : February 10, 2017
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information
First Submitted Date  ICMJE February 8, 2017
First Posted Date  ICMJE February 10, 2017
Last Update Posted Date September 19, 2019
Study Start Date  ICMJE July 2013
Actual Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2017)
Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events [ Time Frame: 24 weeks ]
physiological parameter (for safety, measuring cytokine response, fever, symptoms)
Original Primary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events [ Time Frame: 24 weeks ]
Using CTCAE 4 standard to evaluate the level of adverse events after receiving the cells.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2017)
Anti tumor activity of fourth generation anti CD19 CAR-T cells in patients with relapsed or refractory B cell malignancies [ Time Frame: 1 year ]
scale of CAR copies and leukemic cell burden (for efficacy)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
Anti tumor activity of fourth generation anti CD19 CAR-T cells in patients with relapsed or refractory B cell malignancies [ Time Frame: 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
Official Title  ICMJE A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
Brief Summary The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.
Detailed Description

Background:

T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Activation of T cell response from large tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying T cell costimulatory signals for CD28/CD27 plus an inducible apoptotic caspase 9 gene has been established. The study aims to evaluate the activities of a new CAR gene-modified T cells targeting CD19-positive tumors based on a CD19-specific single chain gene constructed 4SCAR (4SCAR19).

Objective:

To evaluate safety and efficacy of administrating 4SCAR19 T cells to patients with CD19 positive B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.

Eligibility:

Patients older than 6-month-old with CD19 positive B cells malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.

Design:

Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or immunohistochemical staining methods.

Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis, and T cells will be activated and modified to express the 4SCAR19 gene.

On Day -5 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR19 lentiviral transduction. The total cell preparation time is approximately 5-7 days.

Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T cells. The preparative regimen will be based on patient immune condition and consistent with standard chemotherapy conditioning regimen.

Participants will receive an infusion of the modified 4SCAR19 T cells and closely followed up for treatment-related responses.

Participants will be continuously monitored for CAR T cells and clinical responses at present timeline.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-cell Malignancies
Intervention  ICMJE Genetic: Therapeutic 4SCAR19 cells
Autologous 4th generation withdrawal lentiviral-transduced 4S CAR-T19
Study Arms  ICMJE Experimental: Therapeutic 4SCAR19 cells
Patients who have relapsed and refractory B cell leukemia after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells.
Intervention: Genetic: Therapeutic 4SCAR19 cells
Publications * Nair S, Wang JB, Tsao ST, Liu Y, Zhu W, Slayton WB, Moreb JS, Dong L, Chang LJ. Functional Improvement of Chimeric Antigen Receptor Through Intrinsic Interleukin-15Ralpha Signaling. Curr Gene Ther. 2019;19(1):40-53. doi: 10.2174/1566523218666181116093857.

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 9, 2017)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. aged more than 6 months.
  2. malignant B cell surface expression CD19 molecules.
  3. the KPS score over 80 points, and survival time is more than 3 months.
  4. greater Hgb 80 g/L.
  5. no contraindications to solid and cell separation

Exclusion Criteria:

  1. accompanied with other active diseases, the treatment is difficult to correct.
  2. bacteria, fungus, or virus infection, unable to control.
  3. people living with HIV.
  4. active HBV and HCV infection.
  5. of pregnancy and nursing mothers.
  6. before entering the test of the use of glucocorticoid systemic treatment within a week.
  7. confirmed before used CAR - but invalid
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03050190
Other Study ID Numbers  ICMJE GIMI-IRB-16001
Has Data Monitoring Committee Yes
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
Plan to Share IPD: Undecided
Current Responsible Party Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Shenzhen Geno-Immune Medical Institute
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lung-Ji Chang Shenzhen Geno-Immune Medical Institute
PRS Account Shenzhen Geno-Immune Medical Institute
Verification Date September 2019

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