CD19/79b Bi-specific CAR-T Cell Therapy

NCT ID: NCT05436509

Last Updated: 2022-06-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-30
• Study Completion Date: 2026-06-30

Brief Summary

The purpose of this study is to assess the feasibility, safety and efficacy of CD19/79b bi-specific CAR-T cell therapy in patients with CD19 and/or CD79b positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/79b bi-specific CAR-T cells and their persistency in patients.

Detailed Description

Patients with refractory and/or recurrent B cell malignancies have poor prognosis despite complex multimodal therapy. Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Further, more than 40% patients with progressive large B cell lymphoma (LBCL) experienced reduced or lost expression of CD19 on the tumor cells after CAR19 treatment; low surface CD19 density before treatment was associated with progressive disease. Therefore, novel curative approaches are needed. The investigation attempts to use genetically modified T cells to express a 4th generation lentiviral anti-CD19/79b bi-specific CAR (bi-4SCAR-CD19/79b). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD79b, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.

CD79b is a B cell surface antigen, which is a component of B cell receptor. CD79b is up-regulated in more than 90% of B-cell lymphomas. Recent studies have shown that CD79b CAR-T cells have potential in targeting B-cell lymphomas. In addition, several immunotherapy drugs based on targeting CD79b have been reported worldwide. The CD79b specific CAR-T cells with binding moiety of CD79b specific scFv exhibited a high affinity and antitumor effect against CD79b+ tumor cells.

A potential strategy to prevent relapse due to antigen escape is to infuse T-cells capable of recognizing multiple antigens. To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific CD19/79b CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory B cell cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD19 and/or CD79b positive cancer patients.

Conditions

B Cell Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bi-4SCAR-CD19/79b T Cell Therapy for CD19 and/or CD79b positive B cell malignancies

Group Type: EXPERIMENTAL

bi-4SCAR CD19/79b T cells

Intervention Type: BIOLOGICAL

Infusion of bi-4SCAR-CD19/79b T cells at 10\^6 cells/kg body weight via IV

Interventions

bi-4SCAR CD19/79b T cells

Infusion of bi-4SCAR-CD19/79b T cells at 10\^6 cells/kg body weight via IV

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. age older than 6 months.

2. malignant B cell surface expression of CD19 or CD79b molecules.

3. the KPS score over 80 points, and survival time is more than 1 month.

4. greater than Hgb 80 g/L.

5. no contraindications to blood cell collection.

Exclusion Criteria

1. accompanied 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 or HCV infection.

5. pregnant and nursing mothers.

6. under systemic steroid treatment within a week of the treatment.

7. prior failed CD19 and CD79b CAR-T treatment.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

c@szgimi.org

86-0755-86725195

Facility Contacts

Lung-Ji Chang, PhD

Role: primary

c@szgimi.org

86-075586725195

Other Identifiers

GIMI-IRB-22009

Identifier Type: -

Identifier Source: org_study_id