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

Sponsor

Shenzhen Geno-Immune Medical Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT05436509

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
B Cell Malignancies	Biological: bi-4SCAR CD19/79b T cells	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CD19/79b Bi-specific CAR-T Cells Targeting B Cell Malignancies

Anticipated Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bi-4SCAR-CD19/79b T Cell Therapy for CD19 and/or CD79b positive B cell malignancies	Biological: bi-4SCAR CD19/79b T cells Infusion of bi-4SCAR-CD19/79b T cells at 10^6 cells/kg body weight via IV

Arm

Intervention/Treatment

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

Biological: bi-4SCAR CD19/79b T cells

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

Outcome Measures

Primary Outcome Measures

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

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 CAR copies (for efficacy)
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)

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

accompanied with other active diseases and difficult to assess patient response.
bacterial, fungal, or viral infection, unable to control.
living with HIV.
active HBV or HCV infection.
pregnant and nursing mothers.
under systemic steroid treatment within a week of the treatment.
prior failed CD19 and CD79b CAR-T treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong	China	518000

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Shenzhen Geno-Immune Medical Institute

ClinicalTrials.gov Identifier:

NCT05436509

Other Study ID Numbers:

GIMI-IRB-22009

First Posted:

Jun 29, 2022

Last Update Posted:

Jun 29, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Shenzhen Geno-Immune Medical Institute

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Jun 29, 2022