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

Breast Cancer Clinical Trial

Official title: Phase 1 Dose Escalation Study of Systemically Administered IL13Ra2 Chimeric Antigen Receptor (CAR) T Cells After a Nonmyeloablative Conditioning Regimen in Patients With Metastatic Melanoma and Other Solid Tumors

Status Recruiting

Clinical Trial 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 or solid tumors that have spread to other places in the body (metastatic). 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 patient's 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.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the safety of systemic administration of IL13Ralpha2-redirected CAR T cells, including determination of the maximum tolerated dose (MTD).

SECONDARY OBJECTIVES:

I. Clinical response. II. Determine the infiltration of IL13Ralpha2 CAR T cells into the tumor. III. Determine the persistence of IL13Ralpha2 CAR T cells in the peripheral blood.

EXPLORATORY OBJECTIVES:

I. Evaluate the induction of endogenous anti-tumor T cell responses in patients receiving IL13Ralpha2 CAR T cell therapy.

II. Assess for the occurrence of cytokine release syndrome in patients receiving IL13Ralpha2 CAR T cells by evaluating plasma cytokine levels.

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

Patients may receive cyclophosphamide intravenously (IV) over 60 minutes on days -5 to -3 and fludarabine phosphate IV over 15-30 minutes on days -5 to -2. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients also undergo biopsy at baseline and on study, computed tomography (CT), or positron emission tomography (PET) and CT scan at screening and on study, magnetic resonance imaging (MRI) throughout the trial, and collection of blood samples throughout the trial. Patients with disease progression may receive a second cycle with an infusion of IL13Ralpha2 CAR T cells.

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. ;

Related Conditions & MeSH terms

• Acral Melanoma
• Adenocarcinoma of Lung
• Adrenocortical Carcinoma
• Breast Cancer
• Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Lung Adenocarcinoma
• Melanoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Melanoma
• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neuroendocrine Tumor
• Paraganglioma
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Pheochromocytoma
• Recurrent Malignant Solid Neoplasm
• Refractory Malignant Solid Neoplasm
• Skin Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Thyroid Cancer
• Uveal Melanoma

• NCT number: NCT04119024
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Recruiting
• Phase: Phase 1
• Start date: November 27, 2019
• Completion date: October 1, 2025