Fludarabine Followed by Vaccine Therapy and White Blood Cell Infusions in Treating Patients With Unresectable or Metastatic Melanoma
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.
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: keyhole limpet hemocyanin
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
|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|
- 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 ]
- 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 ]
|Study Start Date:||July 2004|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
- 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.
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|
|Principal Investigator:||Walter J. Urba, MD, PhD||Providence Cancer Center, Earle A. Chiles Research Institute|