4SCAR-T Therapy Post CD19-targeted Immunotherapy

CD19 Negative B-cell Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04430530
• Other study ID #: GIMI-IRB-20008
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2020
• 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 (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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• CD19 Negative B-cell Malignancies
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Shenzhen Children's Hospital	Shenzhen	Guangdong
China	The Seventh Affilliated Hospital, Sun Yat-Sen University	Shenzhen	Guangdong
China	Shijiazhuang Zhongxi Children Hospital	Shijiazhuang	Hebei

Sponsors (4)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute	Shenzhen Children's Hospital, ShiJiaZhuang Zhongxi Children Hospital, The Seventh Affilliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells	Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.	24 weeks
Secondary	Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells	Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry	1 year