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

Phase 1

Recruiting

• Conditions: B Cell Malignancies
• Interventions: Biological: bi-4SCAR CD19/79b T cells

• Registration Number: NCT05436509
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

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.

Study Timeline

• Status Verified: 2022-06
• Study First Submitted: 2022-06-22
• Study First Submitted QC: 2022-06-28
• Last Update Submitted: 2022-06-28
• Study First Posted: 2022-06-29
• Last Update Posted: 2022-06-29
• Study Start: 2022-06-30
• Primary Completion: 2025-12-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Safety of fourth generation bi-4SCAR-CD19/79b T cells in patients with B cell malignancies	12 weeks	Safety of fourth generation bi-4SCAR-CD19/79b T cells in patients with B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events standard to evaluate the level of adverse events

Secondary Outcome Measures

Name	Time	Method
Anti tumor activity of fourth generation bi-4SCAR-CD19/79b T cells in patients with relapsed or refractory B cell malignancies	1 year	Scale of leukemic cell burden (for efficacy)

Trial Locations

Locations (1)

Shenzhen Geno-immune Medical Institute; 🇨🇳 Shenzhen, Guangdong, China