NCT03068624

Autologous CD8+ SLC45A2-Specific T Lymphocytes With Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Uveal Melanoma

Phase Ib Study of Cellular Adoptive Immunotherapy Using Autologous Cd8+ Antigen-Specific T Cells and Anti-Ctla4 for Patients With Metastatic Uveal Melanoma

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of autologous CD8 positive (+) SLC45A2-specific T lymphocytes when given together with cyclophosphamide, aldesleukin, and ipilimumab, and to see how well they work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). To make specialized CD8+ T cells, researchers separate out T cells collected from patients' blood and treat them so they are able to target melanoma cells. The blood cells are then given back to the patients. This is known as "adoptive T cell transfer" or "adoptive T cell therapy." Drugs used in chemotherapy, such as cyclophosphamide, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Biological therapies, such as aldesleukin, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving autologous CD8+ SLC45A2-specific T lymphocytes together with cyclophosphamide, aldesleukin, and ipilimumab may work better in treating patients with metastatic uveal melanoma.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of adoptively transferred SLC45A2-specific cytotoxic T-lymphocytes (CTL) for the treatment of patients with metastatic uveal melanoma. SECONDARY OBJECTIVES: I. To establish the anti-tumor efficacy as measured by immune-related response criteria (irRC) and duration of response in metastatic uveal melanoma patients receiving autologous CD8+ T cells against SLC45A2. II. To assess the safety and tolerability of adoptively transferred SLC45A2-specific CTL in combination with immune checkpoint blockade in metastatic uveal melanoma patients. III. To quantify in vivo numeric and functional persistence of transferred CTL, and development of antigen spreading in metastatic uveal melanoma patients. IV. To assess overall survival and progression-free survival in metastatic uveal melanoma patients. OUTLINE: This is a dose escalation study of autologous CD8+ SLC45A2-specific T lymphocytes. PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 30-60 minutes on day -2. T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin twice daily (BID) subcutaneously (SC) for 14 days in the absence of disease progression or unacceptable toxicity. POST T-CELL INFUSION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at days 84 and 168, and then every 3 months for up to 5 years.

Conditions

• Metastatic Malignant Neoplasm in the Liver
• Metastatic Uveal Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	Aldesleukin	Given SC
BIOLOGICAL	Autologous CD8+ SLC45A2-specific T Lymphocytes	Given via hepatic arterial infusion via central catheter
DRUG	Cyclophosphamide	Given IV
BIOLOGICAL	Ipilimumab	Given IV

Timeline

• Start date: 2017-09-08
• Primary completion: 2022-12-31
• Completion: 2025-07-31
• First posted: 2017-03-03
• Last updated: 2024-01-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study