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Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma

2019-10-15 11:11:29 | BioPortfolio

Summary

This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma. The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patients own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.

Description

PRIMARY OBJECTIVE:

I. Safety.

SECONDARY OBJECTIVES:

I. Clinical response. II. Chimeric antigen receptor (CAR) T-cell tumor infiltration and persistence. III. Impact of IL-2 on the persistence and tumor infiltration of IL13Ralpha2 CAR T cells.

EXPLORATORY OBJECTIVES:

I. Cytokine release syndrome analysis. II. Evaluation of endogenous anti-tumor immune response.

OUTLINE: This is a dose-escalation study of IL13Ralpha2-specific hinge-optimized 4-1BB-co-stimulatory CAR/truncated (Cluster of Differentiation 19) CD19-expressing autologous TN/MEM cells (IL13Ralpha2 CAR T cells).

Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients may also receive recombinant interleukin-2 subcutaneously (SC) twice daily (BID) on days 1-7.

After completion of study treatment, patients are followed every 2-3 months for 2 years, every 6 months for 3 years, then every year for at least 15 years.

Study Design

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8 (American Joint Committee on Cancer )

Intervention

Cyclophosphamide, Fludarabine Phosphate, IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells, Recombinant Interleukin-2

Location

City of Hope Comprehensive Cancer Center
Duarte
California
United States
91010

Status

Not yet recruiting

Source

Jonsson Comprehensive Cancer Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-10-15T11:11:29-0400

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Medical and Biotech [MESH] Definitions

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

Immunoglobulin heavy chain gene exons coding for the hinge region of the heavy chains between the first constant region (on the FAB FRAGMENTS) and the second constant region (on the FC FRAGMENTS).

An enzyme of the transferase class that catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 2.2.1.1.

An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 2.2.1.2.

An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and ammonia. This enzyme is specific for arginine biosynthesis or the urea cycle. Absence or lack of this enzyme may cause CARBAMOYL-PHOSPHATE SYNTHASE I DEFICIENCY DISEASE. EC 6.3.4.16.

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In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

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