CD19/70 Bi-specific CAR-T Cell Therapy

Phase 1

Recruiting

• Conditions: B Cell Malignancies
• Interventions: Biological: bi-4SCAR CD19/70 T cells

• Registration Number: NCT05436496
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

Brief Summary

The purpose of this study is to assess the feasibility, safety and efficacy of CD19/70 bi-specific CAR-T cell therapy in patients with CD19 and/or CD70 positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/70 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-CD19/70 bi-specific CAR (bi-4SCAR-CD19/70). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD70, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.

CD70 is highly expressed in many cancers, but limited in normal tissues, it is a potential CAR-T therapeutic target. Expression of CD70 was observed on multiple tumor types including solid tumor as well as B cell malignancies. In addition, it has been reported that anti-CD70 CAR T-cells can eliminate CD70-positive cells and exhibit strong anti-tumor effects in preclinical animal models. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibited a higher affinity and antitumor effect against CD70-positive 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 CD19/70 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 CD70 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: 30

Inclusion Criteria

1. age older than 6 months.
2. malignant B cell surface expression of CD19 or CD70 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 CD70 CAR-T treatment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
bi-4SCAR-CD19/70 T Cell Therapy for CD19 and/or CD70 positive B cell malignancies	bi-4SCAR CD19/70 T cells	-

Primary Outcome Measures

Name	Time	Method
Safety of fourth generation bi-4SCARCD19/70 T cells in patients with B cell malignancies	12 weeks	Safety of fourth generation bi-4SCARCD19/70 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-4SCARCD19/70 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