CAR-T Immunotherapy Targeting CD19- ALL

• Sponsor: Shenzhen Geno-Immune Medical Institute (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04016129
• Collaborator: (none)
• Enrollment: 100
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 53
• Patients Per Site: 33.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
B-cell Leukemia	Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CART Immunotherapy Targeting CD19 Negative Acute Lymphoblastic Leukemia
• Actual Study Start Date: Jul 15, 2019
• Anticipated Primary Completion Date: Jul 15, 2021
• Anticipated Study Completion Date: Dec 15, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety of infusion [24 weeks]

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

Secondary Outcome Measures

1. Anti-tumor activity of CART [1 year]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510282
2	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong	China	518000
3	Zhongxi Children Hospital	Shijiazhuang	Hebei	China	050006

Sponsors and Collaborators

• Shenzhen Geno-Immune Medical Institute

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT04016129
• Other Study ID Numbers: GIMI-IRB-19003
• First Posted: Jul 11, 2019
• Last Update Posted: Sep 19, 2019
• Last Verified: Sep 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Shenzhen Geno-Immune Medical Institute: CD19- B-ALL; CART; CD22, CD123, CD38, CD10, CD20, TSLPR
• Additional relevant MeSH terms: Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

No Results Posted as of Sep 19, 2019