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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


Phase 2
16 Years
N/A
Not Enrolling
Both
Melanoma (Skin)

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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