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

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

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.

Study Overview

• Status: Recruiting
• Conditions: B Cell Malignancies
• Intervention / Treatment: Biological: bi-4SCAR CD19/79b T cells

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-Immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of fourth generation bi-4SCAR-CD19/79b T cells in patients with B cell malignancies	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	12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): June 30, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: June 22, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): June 29, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; CD19; B cell Malignancies; CD79b
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GIMI-IRB-22009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No