Treatment Of Patients With Metastatic Melanoma Using Nonmyeloablative But Lymphocyte Depleting Regimen Followed By The Administration Of In Vitro Sensitized Lymphocytes Reactive With ESO-1 Antigen
- Determine the clinical tumor regression in patients with metastatic melanoma treated
with a lymphocyte-depleting nonmyeloablative preparative chemotherapy regimen followed
by autologous lymphocyte infusion, ESO-1 peptide vaccination comprising ESO-1:157-165
(165V) and Montanide ISA-51, and interleukin-2.
- Determine the survival of the infused lymphocytes in patients treated with this
- Determine the long-term immune status of patients treated with this regimen.
OUTLINE: Patients are stratified according to type of lymphocyte infusion (ESO-1-reactive
tumor-infiltrating lymphocytes [TIL] vs ESO-1 reactive peripheral blood lymphocytes [PBL]).
- Autologous lymphocyte collection and expansion: Autologous PBL or TIL are collected
from patients during leukapheresis or biopsy. The cells are sensitized in vitro with
ESO-1:157-165 (165V) melanoma antigen and expanded.
- Lymphocyte-depleting nonmyeloablative preparative chemotherapy: Patients receive
lymphocyte-depleting nonmyeloablative preparative chemotherapy comprising
cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 15-30 minutes
on days -5 to -1.
- Autologous lymphocyte infusion: Autologous PBL or TIL are reinfused on day 0*. Patients
also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 1 and
continuing until blood counts recover.
- ESO-1 peptide vaccination: Patients receive ESO-1 peptide vaccination comprising
ESO-1:157-165 (165V) peptide emulsified in Montanide ISA-51 SC on days 0*-4, 11, 18,
- Interleukin therapy: Patients receive interleukin-2 IV over 15 minutes 3 times daily on
NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.
Patients achieving stable disease or partial response may receive up to 1 retreatment
course. Patients with progressive disease after infusion of PBL may receive retreatment with
TIL, if available.
Patients are followed at 4-5 weeks, every 3-4 months for 2 years, and then annually
PROJECTED ACCRUAL: A total of 24-74 patients (12-37 per stratum) will be accrued for this
study within 2-3 years.
Masking: Open Label, Primary Purpose: Treatment
Clinical tumor regression
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|
|NCI - Center for Cancer Research||Bethesda, Maryland 20892|