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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079144
First received: March 8, 2004
Last updated: June 18, 2013
Last verified: May 2005
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Clinical tumor regression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival of infused lymphocytes [ Designated as safety issue: No ]
  • Long-term immune status [ Designated as safety issue: No ]

Study Start Date: January 2004
Study Completion Date: August 2005
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079144

Locations
United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00079144     History of Changes
Obsolete Identifiers: NCT00076661
Other Study ID Numbers: CDR0000354491, NCI-04-C-0104, NCI-6233
Study First Received: March 8, 2004
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Freund's Adjuvant
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on July 20, 2014