4SCAR-T Therapy Post CD19-targeted Immunotherapy

Shenzhen Geno-Immune Medical Institute

Status and phase: Unknown; Phase 2; Phase 1

Conditions: CD19 Negative B-cell Malignancies

Treatments: Biological: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20

Study type: Interventional

Funder types: Other

Identifiers

NCT04430530

GIMI-IRB-20008

Details and patient eligibility

About

This study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells (4SCAR-T) targeting CD19-negative B-ALL that express alternative surface antigens such as CD22, CD10, CD20, CD38, and CD123, as many patients relapse after anti-CD19 immunotherapy. Clinical response and optiminzation 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.

Full description

Anti-CD19 immunotherapy based on antibody conjugated drugs or CD19-CAR-T cells has demonstrated unprecedented positive response in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, many patients still relapse and up to 30-50% of those relapses are characterized by the loss of CD19 surface antigen. Patients with CD19-negative relapse 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, the 4th generation CAR gene-modified T cells targeting CD22, CD10, CD20, CD38, or CD123 have been considered in post anti-CD19 treatment. This study aims to evaluate safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to patients with CD19-escaped B cell malignancies.

Enrollment: 100 estimated patients

Sex: All

Ages: 6 months to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age older than 6 months.
2. B cell malignancies relapsed after anti-CD19 immunotherapy.
3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20.
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. Bacterial, fungal, or viral infection 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.
7. Judged difficult to cooporate for continued evaluation.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

4SCAR-CD22/CD123/CD38/CD10/CD20 infusion

Experimental group

Description:

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

Treatment:

Biological: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20