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Cyclophosphamide

Fludarabine

Fludarabine phosphate

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.

Single dose of RPM CD19-mbIL15-CAR-T cells will be infused, and a standard "3+3" design will be applied.

Drug: Fludarabine

Fludarabine is used for lymphodepletion.

Drug: Cyclophosphamide

Cyclophosphamide is used for lymphodepletion

RPM CD19-mbIL15-CAR-T cells

Shangru Wu, PhD

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 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

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

Infusion of CD19-Specific Chimeric Antigen Receptor T-cells Produced by Rapid Personalized Manufacture for Patients With Advanced Lymphoid Malignancies

MTD is the highest dose at which no more than 1 of 6 patients experiences a dose limiting toxicity.

Percentage of subjects for whom the desired dose of RPM CD19 mbIL15 CAR-T cells can be successfully manufactured.

The incidence and severity of AE of Cytokine Release Syndrome and neurotoxicity.

Duration of CAR-T cell persistence by vector copy number (VCN).

Measure the decrease of RPM CD19 mbIL15-CAR-T cells after cetuximab administration.

Immnuogenicity (humoral) defined as the percent of subjects that develop anti-drug antibodies.

levels of cytokine in serum, including IL-6, IL-10, IFN-γ, TNFα concentration (pg/mL), measured by Elisa.

Percent of subjects with measurable RPM CD19 mbIL15 CAR-T cells in bone marrow.

Objective response rate (ORR), complete response (CR), Complete response with incomplete blood count recovery (CRi), partial response (PR)

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 will be determined as time fro the start of RPM CD19-mbIL15-CAR-T cells infusion until death due to any cause.

CD19 expression of tumor tissue when tumor relapse and progress.

Spots Global Cancer Trial Database for cd19 specific car