4SCAR-T Therapy Post CD19-targeted Immunotherapy

Sponsor

Shenzhen Geno-Immune Medical Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04430530

Collaborator

ShiJiaZhuang Zhongxi Children Hospital (Other), Shenzhen Children's Hospital (Other), The Seventh Affiliated Hospital of Sun Yat-sen University (Other)

100

Enrollment

Locations

Arm

Anticipated Duration (Months)

33.3

Patients Per Site

0.8

Patients Per Site Per Month

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 (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.

Condition or Disease	Intervention/Treatment	Phase
CD19 Negative B-cell Malignancies	Biological: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20	Phase 1/Phase 2

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 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:

4SCAR-T Therapy After Anti-CD19 Immunotherapy Targeting B Cell Acute Lymphoblastic Leukemia

Anticipated Study Start Date :

Jun 1, 2020

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

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

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

Biological: 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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Complications with other active diseases, and difficult to assess patient response.
Bacterial, fungal, or viral infection unable to control.
Living with HIV.
Active HBV and HCV infection.
Pregnant and nursing mothers.
Under systemic steroid use within a week of the treatment.
Judged difficult to cooporate for continued evaluation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shenzhen Children's Hospital	Shenzhen	Guangdong	China	518000
2	The Seventh Affilliated Hospital, Sun Yat-Sen University	Shenzhen	Guangdong	China	518107
3	Shijiazhuang Zhongxi Children Hospital	Shijiazhuang	Hebei	China