CAR-T Immunotherapy Targeting CD19- ALL

• ClinicalTrials.gov Identifier: NCT04016129
• Recruitment Status: Unknown
• First Posted: July 11, 2019
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: July 4, 2019
• First Posted Date: July 11, 2019
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: July 15, 2019
• Estimated Primary Completion Date: July 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 9, 2019)

Safety of infusion [ Time Frame: 24 weeks ]

Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 9, 2019)

Anti-tumor activity of CART [ Time Frame: 1 year ]

Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CAR-T Immunotherapy Targeting CD19- ALL
• Official Title: CART Immunotherapy Targeting CD19 Negative Acute Lymphoblastic Leukemia
• Brief Summary: This study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 negative ALL that express CD22, CD123, CD38, CD10, CD20 and TSLPR, as many patients developed CD19-negative disease after CD19 CART immunotherapy. 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

Anti-CD19 chimeric antigen receptor T cell therapy has demonstrated unprecedented treatment responses in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, many studies have reported that a subset of patients still relapse and about 30-50% of those relapses are characterized by the loss of CD19 surface antigen. Patients with CD19-negative relapse after CD19 CAR-T-cell therapy usually have a poor prognosis. The mechanisms underlying CD19-negative relapses are not fully understood and it is important to develop solutions to supplement post-CD19 immunotherapies.

Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population include many known B-cell lineage antigens. To prevent further target escape and improve the therapeutic effects, CAR gene-modified T cells targeting CD22, CD123, CD38, CD10, CD20 or TSLPR have been considered in post CD19 CAR-T immunotherapy. This study aims to evaluate safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to patients with CD19-negative B cell malignancies.

• 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 Leukemia

Intervention

Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR

4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR Patients who have relapsed after CD19 CART immunotherapy or have CD19 negative B cell malignancies

Study Arms

Experimental: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR

Patients who have relapsed after CD19 CART immunotherapy or have CD19 negative B cell malignancies

Intervention: Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 9, 2019): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 15, 2023
• Estimated Primary Completion Date: July 15, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age older than 6 months.
2. Native CD19 negative B cell malignancies or relapse after CD19-CAR-T immunotherapy.
3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20/TSLPR.
4. The KPS score over 80 points, and survival time is more than 1 month.
5. Greater than Hgb 80 g/L.
6. No contraindications to blood cell collection.

Exclusion Criteria:

1. Complications with other active diseases, and difficult to assess patient response.
2. Bacteria, fungus, or virus infection, and unable to control.
3. Living with HIV.
4. Active HBV and HCV infection.
5. Pregnant and nursing mothers.
6. Under systemic steroid use within a week of the treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 75 Years (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: NCT04016129
• Other Study ID Numbers: GIMI-IRB-19003
• Has Data Monitoring Committee: Not Provided

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: Not Provided
• Current Responsible Party: 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, PhD; Shenzhen Geno-Immune Medical Institute

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