NCT00085462

Gene-Modified White Blood Cells Followed By Interleukin-2 and Vaccine Therapy in Treating Patients With Metastatic Melanoma

Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 61 (estimated)
• Sponsor: National Institutes of Health Clinical Center (CC) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Vaccines may make the body build an immune response to kill tumor cells. Combining gene-modified white blood cell infusions with interleukin-2 and vaccine therapy may kill more tumor cells. PURPOSE: This phase I trial is studying how well giving gene-modified white blood cells when given together with interleukin-2 and vaccine therapy works in treating patients with metastatic melanoma.

Detailed description

OBJECTIVES: Primary * Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+ autologous peripheral blood lymphocytes followed by interleukin-2. Secondary * Determine the in vivo survival of TCR gene-engineered cells in patients treated with this regimen. OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (TIL) (yes vs no). Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1. * Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0\*. * Stratum 2 (CD8+peripheral blood lymphocytes \[PBL\]): Patients receive CD8+PBL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0\*. NOTE: \*Day 0 is 1-4 days after the last dose of fludarabine. Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable or responding disease may receive 1 retreatment course. Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter. PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.

Conditions

• Melanoma (Skin)

Interventions

Type	Name	Description
BIOLOGICAL	aldesleukin
BIOLOGICAL	filgrastim
BIOLOGICAL	gp100-fowlpox vaccine
BIOLOGICAL	therapeutic autologous lymphocytes
BIOLOGICAL	therapeutic tumor infiltrating lymphocytes
DRUG	cyclophosphamide
DRUG	fludarabine phosphate

Timeline

• Start date: 2004-05-01
• Primary completion: 2007-05-01
• Completion: 2008-09-01
• First posted: 2004-06-11
• Last updated: 2012-06-22

Locations

2 sites across 1 country: United States