CAR-T Immunotherapy Targeting CD19- ALL

B-cell Leukemia Clinical Trial

Official title:

CART Immunotherapy Targeting CD19 Negative Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04016129
• Other study ID #: GIMI-IRB-19003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 15, 2019
• Est. completion date: December 15, 2023

Study information

• Verified date: September 2019
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, PhD
• Phone: +86-0755 8672-5195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 15, 2023
• Est. primary completion date: July 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Leukemia
• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell

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

Locations

Country	Name	City	State
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong
China	Zhongxi Children Hospital	Shijiazhuang	Hebei

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of infusion	Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.	24 weeks
Secondary	Anti-tumor activity of CART	Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry	1 year