Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Lymphocyte-Depleting Nonmyeloablative Preparative Chemotherapy Followed By Autologous Lymphocyte Infusion, Peptide Vaccine Plus Montanide ISA-51, and Interleukin-2 in Treating Patients With Metastatic Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 16 and over NCI NCI-04-C-0104 NCI-6233, 6233, NCT00079144

Objectives

Primary

1. 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

1. Determine the survival of the infused lymphocytes in patients treated with this regimen.
2. Determine the long-term immune status of patients treated with this regimen.

Entry 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

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

Patient Characteristics:

Age

• 16 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm³
• Platelet count > 100,000/mm³
• 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

• FEV₁ > 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

Expected Enrollment

A total of 24-74 patients (12-37 per stratum) will be accrued for this study within 2-3 years.

Outcomes

Clinical tumor regression

Survival of infused lymphocytes
Long-term immune status

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Steven Rosenberg, MD, PhD, Protocol chair		Ph: 866-820-4505 Email: sar@nih.gov

Registry Information
Official Title		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
Trial Start Date		2004-01-28
Registered in ClinicalTrials.gov		NCT00079144
Date Submitted to PDQ		2004-01-26
Information Last Verified		2005-05-18