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
16 Years
N/A
Both
Melanoma (Skin)
Trial Information
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
OBJECTIVES:
Primary
- 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.
Secondary
- Determine the survival of the infused lymphocytes in patients treated with this
regimen.
- 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,
and 25.
- Interleukin therapy: Patients receive interleukin-2 IV over 15 minutes 3 times daily on
days 0*-4.
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
thereafter.
PROJECTED ACCRUAL: A total of 24-74 patients (12-37 per stratum) will be accrued for this
study within 2-3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of metastatic melanoma that is refractory to standard therapy (including
high-dose interleukin-2)
- Measurable disease
- HLA-A*0201 positive
- Epstein-Barr virus positive
- ESO-1-expressing disease by reverse transcription polymerase chain reaction amplified
tissue OR presence of ESO-1 serum antibody
PATIENT CHARACTERISTICS:
Age
- 16 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
- Hemoglobin > 8.0 g/dL
Hepatic
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
- AST and ALT < 3 times upper limit of normal
- Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL for patients with Gilbert's syndrome)
- No coagulation disorders
Renal
- Creatinine ≤ 2.0 mg/dL
Cardiovascular
- No prior myocardial infarction
- No major cardiovascular illness by stress thallium or comparable test
- No cardiac arrhythmias
- LVEF ≥ 45%
- Normal cardiac stress test required for the following conditions:
- Prior EKG abnormalities
- Symptoms of cardiac ischemia
- Arrhythmias
- Age 50 and over
Pulmonary
- FEV_1 > 60% of predicted (for patients with a prolonged history of cigarette smoking
or symptoms of respiratory dysfunction)
- No obstructive or restrictive pulmonary disease
- No other major respiratory illness
Immunologic
- HIV negative
- No active systemic infection
- No opportunistic infection
- No major immune system illness
- No form of primary or secondary immunodeficiency
- No known hypersensitivity to study agents
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 4 months
after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- Prior ESO-1-based vaccination allowed
Chemotherapy
- At least 6 weeks since prior nitrosoureas and recovered
Endocrine therapy
- No concurrent systemic steroid therapy
Radiotherapy
- Recovered from prior radiotherapy
Surgery
- Not specified
Other
- At least 4 weeks since prior systemic therapy
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical tumor regression
Safety Issue:
No
Principal Investigator
Steven A. Rosenberg, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
NCI - Surgery Branch
Authority:
United States: Federal Government
Study ID:
CDR0000354491
NCT ID:
NCT00079144
Start Date:
January 2004
Completion Date:
August 2005
Related Keywords:
- Melanoma (Skin)
- recurrent melanoma
- stage IV melanoma
- Melanoma
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
| NCI - Center for Cancer Research | Bethesda, Maryland 20892 |
