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

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

Tracking Information

• First Submitted Date: February 8, 2017
• First Posted Date: February 10, 2017
• Last Update Posted Date: September 19, 2019
• Study Start Date: July 2013
• Actual Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-cell Malignancies

Intervention

Genetic: Therapeutic 4SCAR19 cells

Autologous 4th generation withdrawal lentiviral-transduced 4S CAR-T19

Study Arms

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.

Recruitment Information

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

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03050190
• Other Study ID Numbers: 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

• 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: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019