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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
B-cell Malignancies Genetic: Therapeutic 4SCAR19 cells Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
Study Start Date : July 2013
Actual Primary Completion Date : July 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scars

Arms and Interventions
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Arm Intervention/treatment
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.
 Genetic: Therapeutic 4SCAR19 cells
Autologous 4th generation withdrawal lentiviral-transduced 4S CAR-T19


Outcome Measures
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Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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)


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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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): NCT03050190


Contacts
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Contact: Lung-Ji Chang, PhD +86-0755 8672-5195 c@szgimi.org

Locations
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China, Guangdong
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, PhD    +86-13671121909    c@szgimi.org   
China, Yunnan
The First People's Hospital of Yunnan Recruiting
Kunming, Yunnan, China, 650000
Contact: Xun Lai, MD    13577096609    1729112214@qq.com   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
Investigators
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Principal Investigator: Lung-Ji Chang Shenzhen Geno-Immune Medical Institute
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute
ClinicalTrials.gov Identifier: NCT03050190    
Other Study ID Numbers: GIMI-IRB-16001
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:
CART therapy
4SCAR19
CD19
B cell leukemia
B-ALL
Additional relevant MeSH terms:
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Neoplasms