4SCAR-T Therapy Post CD19-targeted Immunotherapy

Phase 1

• Conditions: CD19 Negative B-cell Malignancies
• Interventions: Biological: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20

• Registration Number: NCT04430530
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2020-06
• Study Start: 2020-06-01
• Study First Submitted: 2020-06-09
• Study First Submitted QC: 2020-06-10
• Last Update Submitted: 2020-06-10
• Study First Posted: 2020-06-12
• Last Update Posted: 2020-06-12
• Primary Completion: 2023-05-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
4SCAR-CD22/CD123/CD38/CD10/CD20 infusion	Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20	Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies

Primary Outcome Measures

Name	Time	Method
Safety of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells	24 weeks	Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.

Secondary Outcome Measures

Name	Time	Method
Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells	1 year	Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry

Trial Locations

Locations (3)

Shijiazhuang Zhongxi Children Hospital; 🇨🇳 Shijiazhuang, Hebei, China

Shenzhen Children's Hospital; 🇨🇳 Shenzhen, Guangdong, China

The Seventh Affilliated Hospital, Sun Yat-Sen University; 🇨🇳 Shenzhen, Guangdong, China