Fludarabine Followed by Vaccine Therapy and White Blood Cell Infusions in Treating Patients With Unresectable or Metastatic Melanoma

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: September 7, 2004
Last updated: April 2, 2013
Last verified: August 2009

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Infusions of a person's white blood cells may be able to replace immune cells that were destroyed by chemotherapy. Combining fludarabine with vaccine therapy and white blood cell infusions may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects of giving vaccine therapy together with fludarabine and white blood cell infusions and to see how well it works in treating patients with unresectable or metastatic melanoma.

Condition Intervention Phase
Melanoma (Skin)
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: keyhole limpet hemocyanin
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Pilot Trial of Therapeutic Vaccination With a Modified gp100 Melanoma Peptide (gp100:209-217(210M)), Montanide ISA 51, and KLH With Reconstitution After Chemotherapy to Induce Lymphopenia in Patients With Metastatic Melanoma

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Toxicity by clinical and laboratory observation at 1 month [ Designated as safety issue: Yes ]
  • Antigen-specific T-cell responses by tetramer analysis, ELISPOT, and cytokine flow cytometry periodically [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare 2 different dosing schedules of fludarabine in terms of lymphocyte recovery using a complete blood count periodically [ Designated as safety issue: No ]
  • Tumor regression by standard imaging at study completion [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2004
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Detailed Description:



  • Determine the toxicity and immune effects of vaccination comprising modified gp100 peptide (gp100:209-217[210M]), Montanide ISA-51, and keyhole limpet hemocyanin followed by peripheral blood mononuclear cell reinfusion after treatment-induced lymphopenia with fludarabine in patients with unresectable or metastatic melanoma.
  • Determine the induction of antigen-specific T-cell responses in patients treated with this regimen.
  • Determine the kinetics and duration of immune response in patients treated with this regimen.
  • Compare the immunologic effects of this regimen in these patients with historical results.


  • Compare 2 different dosing schedules of fludarabine, in terms of induction of lymphopenia and granulocytopenia and on the induction of a specific immune response to this vaccine, in these patients.

OUTLINE: This is a pilot, randomized study. Patients are randomized to 1 of 2 treatment arms.

Within 2 weeks before the start of fludarabine, all patients undergo leukapheresis over 4-6 hours for the collection of peripheral blood mononuclear cells (PBMCs).

  • Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5.
  • Arm II: Patients receive fludarabine as in arm I on days 1, 3, and 5. In both arms, patients receive autologous PBMCs IV over approximately 30 minutes on day 8 and vaccination comprising gp100:209-217(210M) peptide, Montanide ISA-51, and keyhole limpet hemocyanin subcutaneously on days 8, 22, 36, 50, and 64. Patients with stable or responding disease continue to receive vaccination on day 78 and then every 28-31 days for up to 1 year.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study within 2 years.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed malignant melanoma

    • Metastatic or unresectable disease
  • Measurable disease
  • HLA-A2 positive
  • Received at least 1 prior immunotherapy and/or chemotherapy regimen for metastatic disease (first 6 patients only)
  • No known brain metastases unless previously treated with radiotherapy and/or surgery AND is stable for at least 1 month after treatment



  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months


  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Absolute lymphocyte count ≥ 500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusions allowed)
  • Hematocrit ≥ 24%
  • No other active bleeding


  • Bilirubin < 2 times upper limit of normal (ULN) (unless due to Gilbert's disease)
  • AST and ALT < 3 times ULN
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative


  • Creatinine < 2 mg/dL
  • No uncontrolled hypercalcemia


  • No uncontrolled symptomatic congestive heart failure
  • No unstable angina pectoris
  • No uncontrolled cardiac arrhythmia
  • No uncontrolled hypertension


  • No uncontrolled bronchospasm
  • No hemoptysis


  • Negative serology for all of the following:

    • HIV-1 and HIV-2
    • HTLV-1 and -2
    • Syphilis
  • Rheumatoid factor < 43 units/μL
  • Anti-nuclear antibody < 11 units/μL
  • No history of multiple sclerosis, systemic lupus erythematosus, or myasthenia gravis
  • No primary or secondary immunodeficiency
  • No active infection
  • No allergy to seafood or shellfish that would preclude study participation


  • No active gastrointestinal bleeding
  • No uncontrolled hyperglycemia
  • No other medical or psychiatric condition or social situation that would preclude study compliance
  • No other uncontrolled illness
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3-4 months after study participation


Biologic therapy

  • See Disease Characteristics
  • No prior immunization with gp100:209-217(210M) peptide


  • See Disease Characteristics
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

  • More than 2 weeks since prior steroid therapy except replacement steroids or inhaled steroids
  • No concurrent corticosteroids except replacement steroids
  • No concurrent dexamethasone


  • See Disease Characteristics
  • More than 2 weeks since prior radiotherapy


  • See Disease Characteristics
  • Recovered from prior surgery


  • No other concurrent investigational agents
  • No other concurrent anticancer 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: NCT00091143

United States, Oregon
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213-2967
Sponsors and Collaborators
Providence Cancer Center, Earle A. Chiles Research Institute
National Cancer Institute (NCI)
Principal Investigator: Walter J. Urba, MD, PhD Providence Cancer Center, Earle A. Chiles Research Institute
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00091143     History of Changes
Other Study ID Numbers: CDR0000383908  PPMC-IRB-02-99  NCI-6361 
Study First Received: September 7, 2004
Last Updated: April 2, 2013
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Fludarabine phosphate
Freund's Adjuvant
Keyhole-limpet hemocyanin
Adjuvants, Immunologic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on February 11, 2016