RPM CD19-mbIL15-CAR-T Cells in Patient With Advanced Lymphoid Malignancies

Phase 1

Terminated

• Conditions: Non-Hodgkin's Lymphoma Refractory; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma, Relapsed; Primary Mediastinal Large B Cell Lymphoma; B-cell Acute Lymphoblastic Leukemia; Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma
• Interventions: Biological: RPM CD19-mbIL15-CAR-T cells

• Registration Number: NCT04844086
• Lead Sponsor: Eden BioCell Ltd.

Brief Summary

This is an open-label Phase 1 study to determine the feasibility, safety, and the recommended maximum tolerated Dose (MTD) of a single infusion of RPM CD19 mbIL15 CAR-T cells for adult patients. Approximately 24 subjects will be enrolled and it is anticipated approximately 16 subjects will be infused at the varied doses of T cells.

Detailed Description

This is an open-label Phase 1 study to determine the feasibility, safety, and the recommended maximum tolerated Dose (MTD) of a single infusion of RPM CD19 mbIL15 CAR-T cells for adult patients. Approximately 24 subjects will be enrolled and it is anticipated approximately 16 subjects will be infused at the varied doses of T cells.

This study will very rapidly administer T cells that are genetically modified by electroporation using DNA plasmids from the SB system to co-express CD19RCD8CD28 (the CAR), mbIL15, and HER1t. The presence of mbIL15 may allow for reduced doses of CAR-T cells to be infused to reduce the risk for adverse events, such as cytokine release syndrome (CRS).

The key features of study design are listed below.

1. Uncontrolled

2. Blinding: open-label

3. Randomized: no

4. Duration of treatment: single infusion within day

5. Titration: none

6. Single center, Taiwan

Study Timeline

• Study Start: 2021-03-02
• Study First Submitted: 2021-04-06
• Study First Submitted QC: 2021-04-08
• Study First Posted: 2021-04-14
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-11
• Primary Completion: 2022-05-12
• Study Completion: 2022-05-12
• Last Update Posted: 2022-05-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Infusion RPM CD19-mbIL15-CAR-T cell	RPM CD19-mbIL15-CAR-T cells	In this study, anti-CD19 autologous chimeric antigen receptor T-cells infusion produced by rapid personalized manufacture are used to treat patients with relapsed/refractory Advanced Lymphoid Malignancies. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to RPM CD19-mbIL15-CAR-T cell infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

Primary Outcome Measures

Name	Time	Method
Maximun Tolerated Dose (MTD) of the RPM CD19- mbIL15-CAR-T	within 4 weeks after infusion	MTD is the highest dose at which no more than 1 of 6 patients experiences a dose limiting toxicity.

Secondary Outcome Measures

Name	Time	Method
Feasibility of the product manufacturing process	day 0 to month 12	Percentage of subjects for whom the desired dose of RPM CD19 mbIL15 CAR-T cells can be successfully manufactured.
Adverse events related to treatment	day 0 to month 12	The incidence and severity of AE of Cytokine Release Syndrome and neurotoxicity.
Persistence of infused T cells	day 0 to month 12	Duration of CAR-T cell persistence by vector copy number (VCN).
Safety Switch Function	day 0 to month 12	Measure the decrease of RPM CD19 mbIL15-CAR-T cells after cetuximab administration.
Immunogenicity	day 0 to month 12	Immnuogenicity (humoral) defined as the percent of subjects that develop anti-drug antibodies.
Cytokine Profile	day 0 to month 12	levels of cytokine in serum, including IL-6, IL-10, IFN-γ, TNFα concentration (pg/mL), measured by Elisa.
Homing ability of the infused T-cells	day 0 to month 12	Percent of subjects with measurable RPM CD19 mbIL15 CAR-T cells in bone marrow.
Disease response after T cell infusion	day 0 to month 12	Objective response rate (ORR), complete response (CR), Complete response with incomplete blood count recovery (CRi), partial response (PR)
Progression-Free Survival	day 0 to month 12	Measured from infusion of RPM CD19 mbIL15 CAR-T cells until the documentation of disease progression or death due to any cause, whichever occurs first.
Overall Survival	day 0 to month 12	Overall survival will be determined as time fro the start of RPM CD19-mbIL15-CAR-T cells infusion until death due to any cause.
Emergence of CD19neg malignant B cells	day 0 to month 12	CD19 expression of tumor tissue when tumor relapse and progress.

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan