Cyclophosphamide and Fludarabine Followed by Vaccine Therapy, Gene-Modified White Blood Cell Infusions, and Aldesleukin 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: NCT00091104
Recruitment Status : Completed
First Posted : September 8, 2004
Last Update Posted : March 15, 2012
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: MART-1:27-35 peptide vaccine Biological: aldesleukin Biological: filgrastim Biological: incomplete Freund's adjuvant Biological: therapeutic autologous lymphocytes Biological: therapeutic tumor infiltrating lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate Procedure: autologous hematopoietic stem cell transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation Radiation: total-body irradiation Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study in Metastatic Melanoma Using a Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 TCR-Gene Engineered Lymphocytes and Subsequent Peptide Immunization
Study Start Date : July 2004
Actual Primary Completion Date : August 2010
Actual Study Completion Date : October 2010

Primary Outcome Measures :
  1. Safety
  2. Tumor regression

Secondary Outcome Measures :
  1. In vivo survival of transplanted cells
  2. Clinical response

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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


  • Diagnosis of metastatic melanoma
  • HLA-A*0201-positive disease
  • Measurable disease
  • Refractory to standard therapy, including high-dose aldesleukin therapy



  • 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 disorder


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


  • Creatinine ≤ 1.6 mg/dL


  • No myocardial infarction
  • No cardiac arrhythmias
  • No cardiac ischemia
  • LVEF ≥ 45% by stress cardiac test* (for patients ≥ 50 years of age OR those with a history of EKG abnormalities)
  • No other major cardiovascular illness by stress thallium or comparable test NOTE: *Stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test


  • No major respiratory illness
  • No obstructive or restrictive pulmonary disease
  • FEV_1 ≥ 60% of predicted on pulmonary function test*
  • DLCO ≥ 60% predicted (for total-body irradiation cohort) NOTE: *For patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction


  • HIV negative
  • No major immune system illness
  • No active systemic infection or opportunistic infection
  • No primary immunodeficiency (e.g., autoimmune colitis or Crohn's disease)
  • No secondary immunodeficiency (e.g., due to chemotherapy or radiotherapy)
  • No history of severe immediate hypersensitivity reaction to study drugs


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 months after completion of study treatment
  • Must sign a durable power of attorney


Biologic therapy

  • See Disease Characteristics
  • Recovered from prior immunotherapy
  • Prior immunization to melanoma antigens allowed

    • Progressive disease during prior immunization allowed
  • Prior cellular therapy, including vector transduction with or without myeloablation, allowed
  • More than 6 weeks since prior anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibody (MDX-010) therapy
  • No prior anti-CTLA-4 antibody unless a post anti-CTLA-4 antibody treatment colonoscopy was normal by biopsy


  • Recovered from prior chemotherapy

Endocrine therapy

  • No concurrent systemic steroids


  • Recovered from prior radiotherapy
  • No prior significant mediastinal or lung radiation (for total-body irradiation cohort)


  • Not specified


  • More than 4 weeks since 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): NCT00091104

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)
Principal Investigator: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch Identifier: NCT00091104     History of Changes
Obsolete Identifiers: NCT00088439
Other Study ID Numbers: 040251
First Posted: September 8, 2004    Key Record Dates
Last Update Posted: March 15, 2012
Last Verified: March 2012

Keywords provided by National Institutes of Health Clinical Center (CC):
stage IV melanoma
recurrent 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
Antimetabolites, Antineoplastic
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic