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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00079144
Recruitment Status : Completed
First Posted : March 10, 2004
Last Update Posted : June 19, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Treating a person's lymphocytes in the laboratory and reinfusing them may replace immune cells destroyed by chemotherapy. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Giving a vaccine with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Interleukin-2 may stimulate a person's lymphocytes to kill tumor cells.

PURPOSE: This phase II trial is studying how well lymphocyte-depleting nonmyeloablative (not damaging to bone marrow) chemotherapy followed by autologous lymphocyte infusion, peptide vaccine plus Montanide ISA-51, and interleukin-2 works in treating patients with metastatic melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: NY-ESO-1 peptide vaccine Biological: aldesleukin Biological: filgrastim Biological: incomplete Freund's adjuvant Biological: therapeutic autologous lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate Phase 2

Detailed Description:



  • 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 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.

Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2004
Actual Study Completion Date : August 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Primary Outcome Measures :
  1. Clinical tumor regression

Secondary Outcome Measures :
  1. Survival of infused lymphocytes
  2. Long-term immune status

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 16 and over

Performance status

  • ECOG 0-1

Life expectancy

  • More than 3 months


  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 8.0 g/dL


  • 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


  • Creatinine ≤ 2.0 mg/dL


  • 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


  • 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


  • 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


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 4 months after study participation


Biologic therapy

  • See Disease Characteristics
  • Prior ESO-1-based vaccination allowed


  • At least 6 weeks since prior nitrosoureas and recovered

Endocrine therapy

  • No concurrent systemic steroid therapy


  • Recovered from prior radiotherapy


  • Not specified


  • At least 4 weeks since prior systemic therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00079144

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Study Chair: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch Identifier: NCT00079144     History of Changes
Obsolete Identifiers: NCT00076661
Other Study ID Numbers: CDR0000354491
First Posted: March 10, 2004    Key Record Dates
Last Update Posted: June 19, 2013
Last Verified: May 2005

Keywords provided by National Cancer Institute (NCI):
recurrent melanoma
stage IV melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Fludarabine phosphate
Freund's Adjuvant
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Adjuvants, Immunologic