Vaccine Therapy and Autologous Lymphocyte Infusion With or Without Fludarabine in Treating Patients With Metastatic Melanoma
Summary
RATIONALE: Vaccines made from a person's dendritic cells that have been treated in the laboratory may help the body build an effective immune response to kill tumor cells. Giving an infusion of autologous lymphocytes and then infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy and autologous lymphocyte infusion together with fludarabine may kill more tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of fludarabine followed by autologous lymphocyte infusion and vaccine therapy and to see how well it works in treating patients with metastatic melanoma.
Description
OBJECTIVES:
Primary
- Assess the toxicity and immune responses in HLA-A*0201-positive patients with chemotherapy-naïve metastatic melanoma treated with either escalating doses of fludarabine or no fludarabine followed by autologous lymphocyte infusion and vaccination with dendritic cells matured ex vivo with a cytokine cocktail and pulsed with MART-1/gp100/tyrosinase/NY-ESO-1/MAGE-3 class I and II peptides.
Secondary
- Compare clinical responses in patients receiving these regimens.
OUTLINE: This is a randomized, controlled, multicenter, dose-escalation study of fludarabine. Patients are randomized to 1 of 2 treatment arms.
All patients undergo two apheresis procedures, one to collect lymphocytes for the autologous lymphocyte infusion and one to collect dendritic cells (DC) for the production of the autologous vaccine. Autologous DC are pulsed with tumor antigen class I and II peptides derived from MART-1, gp100, tyrosinase, NY-ESO-1, and MAGE-3 and matured with a cytokine cocktail comprising tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and prostaglandin E2.
- Arm I: Patients receive fludarabine IV over 30 minutes on days -7 to -3 (beginning 3 days after the second apheresis procedure). Patients receive autologous lymphocyte infusion IV over 1 hour on day 0 followed by vaccination with autologous peptide-pulsed DC intranodally over 24 hours on days 1, 8, 22, and 36. Patients who have stable disease or who achieve a response to treatment may receive re-treatment with fludarabine, autologous lymphocyte infusion, and autologous peptide-pulsed DC vaccine (as above) approximately 4 weeks to 6 months after the last DC vaccine.
Cohorts of 3-12 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 3 of 12 patients experience dose-limiting toxicity.
- Arm II: Patients receive autologous lymphocyte infusion and vaccination with autologous peptide-pulsed DC as in arm I. Patients who have stable disease or who achieve a response to treatment may receive re-treatment with autologous lymphocyte infusion and autologous peptide-pulsed DC vaccine (as in arm I) approximately 4 weeks to 6 months after the last DC vaccine.
After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Study Design
Allocation: Randomized, Control: Active Control, Primary Purpose: Treatment
Conditions
Intraocular Melanoma
Intervention
dendritic cell vaccine therapy, therapeutic autologous lymphocytes, fludarabine phosphate
Location
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa
Florida
United States
33612-9497
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00313508
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Antigens, Cd70
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.
Poliovirus Vaccine, Oral
A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)
Antigen-presenting Cells
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Pertussis Vaccine
A suspension of killed Bordetella pertussis organisms, used for immunization against pertussis (WHOOPING COUGH). It is generally used in a mixture with diphtheria and tetanus toxoids (DTP). There is an acellular pertussis vaccine prepared from the purified antigenic components of Bordetella pertussis, which causes fewer adverse reactions than whole-cell vaccine and, like the whole-cell vaccine, is generally used in a mixture with diphtheria and tetanus toxoids. (From Dorland, 28th ed)
Langerhans Cells
Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.
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