Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
- 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.
- Determine the in vivo survival of TCR gene-engineered cells in patients treated with
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.
Masking: Open Label, Primary Purpose: Treatment
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|
|NCI - Surgery Branch||Bethesda, Maryland 20892-1201|