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Gene-Modified White Blood Cells Followed By Interleukin-2 and Vaccine Therapy 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: NCT00085462
Recruitment Status : Completed
First Posted : June 11, 2004
Last Update Posted : June 22, 2012
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Vaccines may make the body build an immune response to kill tumor cells. Combining gene-modified white blood cell infusions with interleukin-2 and vaccine therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying how well giving gene-modified white blood cells when given together with interleukin-2 and vaccine therapy works in treating patients with metastatic melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: aldesleukin Biological: filgrastim Biological: gp100-fowlpox vaccine Biological: therapeutic autologous lymphocytes Biological: therapeutic tumor infiltrating lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate Phase 1

Detailed Description:



  • Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+ autologous peripheral blood lymphocytes followed by interleukin-2.


  • Determine the in vivo survival of TCR gene-engineered cells in patients treated with this regimen.

OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (TIL) (yes vs no).

Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.

  • Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
  • Stratum 2 (CD8+peripheral blood lymphocytes [PBL]): Patients receive CD8+PBL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.

NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.

Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.

Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable or responding disease may receive 1 retreatment course.

Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
Study Start Date : May 2004
Actual Primary Completion Date : May 2007
Actual Study Completion Date : September 2008

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of melanoma

    • Metastatic disease
  • Measurable disease
  • Refractory to standard therapy, including high-dose interleukin-2 therapy
  • HLA-A*0201 positive
  • Progressive disease during prior immunization to melanoma antigens OR prior treatment with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) cellular therapy with or without myeloablation allowed provided toxicity resolved to ≤ grade 2 (except vitiligo) AND patient does not require systemic steroids
  • No brain metastases



  • 18 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
  • Lymphocyte count > 500/mm^3
  • WBC > 3,000/mm^3
  • No coagulation disorders


  • AST and ALT < 3 times upper limit of normal (ULN)
  • Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL in patients with Gilbert's syndrome)
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative (unless antigen negative)


  • Creatinine ≤ 1.6 mg/dL


  • LVEF ≥ 45% by cardiac stress test

    • No LVEF < 45% in patients ≥ 50 years of age
  • No myocardial infarction
  • No cardiac arrhythmias
  • No symptomatic cardiac ischemia
  • No prior EKG abnormalities
  • No other major cardiovascular illness


  • FEV_1 ≥ 60% of predicted AND no obstructive or restrictive pulmonary disease
  • No symptoms of respiratory dysfunction
  • No other major respiratory illness


  • HIV negative
  • Epstein-Barr virus positive
  • No active systemic infections (including opportunistic infections)
  • No form of primary (e.g., autoimmune colitis or Crohn's disease) or secondary immunodeficiency (due to chemotherapy or radiotherapy)
  • No prior severe immediate hypersensitivity reaction to any of the study agents including eggs
  • No other major illness of the immune system


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 month after study participation
  • Willing to complete a durable power of attorney (DPA)


Biologic therapy

  • See Disease Characteristics
  • More than 6 weeks since prior MDX-010


  • Not specified

Endocrine therapy

  • See Disease Characteristics
  • No concurrent systemic steroid therapy


  • Not specified


  • Not specified


  • More than 4 weeks since other prior systemic therapy and recovered

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): NCT00085462

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United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
NCI - Surgery Branch
Bethesda, Maryland, United States, 20892-1201
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
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Principal Investigator: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch

Layout table for additonal information Identifier: NCT00085462     History of Changes
Obsolete Identifiers: NCT00082264
Other Study ID Numbers: 040181
First Posted: June 11, 2004    Key Record Dates
Last Update Posted: June 22, 2012
Last Verified: June 2012
Keywords provided by National Institutes of Health Clinical Center (CC):
recurrent melanoma
stage IV melanoma
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Fludarabine phosphate
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