NCT01955460

Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma

A Pilot Study of Lymphodepletion Plus Adoptive Cell Transfer With TGF-Beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 12 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This pilot phase I trial studies the side effects and best dose of genetically modified T-cells followed by aldesleukin in treating patients with stage III-IV melanoma. T-cells are a type of white blood cell that help the body fight infections. Genes that may help the T-cells recognize melanoma cells are placed into the T-cells in the laboratory. Adding these genes to the T cells may help them kill more tumor cells when they are put back in the body. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells.

Detailed description

PRIMARY OBJECTIVES: Primary for Cohort A: I. To assess the feasibility and safety of autologous transforming growth factor beta (TGFb) resistant (DNRII transduced) and NGFR transduced tumor infiltrating lymphocytes (TIL) in patients with metastatic melanoma. Primary for Cohort B: I. To assess the feasibility and safety of autologous TGBβ resistant (DNRII transduced) TIL in patients with metastatic melanoma. Feasibility will be defined as the production of virally transduced T cells and treatment of patients with these cells SECONDARY OBJECTIVES: Secondary for Cohort A: I. To determine the survival and immune function of TGFb resistant (DNRII transduced) TIL in vivo. II. To assess the anti-tumor effects of TGFb resistant (DNRII transduced) TIL. Secondary for Cohort B: I. To determine the survival and immune function of TGFβ resistant (DNRII transduced) TIL in vivo II. To assess the anti-tumor effects of TGFβ resistant (DNRII transduced) TIL. OUTLINE: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses). After completion of study treatment, patients are followed up at 6 and 12 weeks, every 3 months for 1 year and then yearly for 10 years.

Conditions

• Metastatic Melanoma
• Stage III Cutaneous Melanoma AJCC v7
• Stage IIIA Cutaneous Melanoma AJCC v7
• Stage IIIB Cutaneous Melanoma AJCC v7
• Stage IIIC Cutaneous Melanoma AJCC v7
• Stage IV Cutaneous Melanoma AJCC v6 and v7

Interventions

Type	Name	Description
BIOLOGICAL	Aldesleukin	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	NGFR-transduced Autologous T Lymphocytes	Given IV
BIOLOGICAL	TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes	Given IV

Timeline

• Start date: 2014-10-15
• Primary completion: 2027-10-30
• Completion: 2027-10-30
• First posted: 2013-10-07
• Last updated: 2026-04-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study