Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
RATIONALE: Vaccines made from a person's dendritic cells mixed with tumor peptides and proteins may help the body build an effective immune response to kill tumor cells. Infusing the vaccine directly into the lymphatic system may cause a stronger immune response and kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of two dendritic cell vaccines in treating patients with stage III or stage IV melanoma.
Biological: polarized dendritic cells
Biological: non-polarized dendritic cells
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma|
- Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
- Assess immune responses to each dendritic cell vaccine outcome [ Time Frame: 7 ] [ Designated as safety issue: No ]
i. Peripheral blood CD8+ and CD4+ T cell responses against HLA-presented melanoma epitopes, and (in patients with available tumor tissue) against autologous tumor cells, and using IFNγ-, and IL-5- ELISPOT assays. CD8+ T cell responses (IFNγ ELISPOT) will be used as a secondary readout: the sum of the specific ELISPOT counts obtained (at week 8) with each of the individual HLA-A2-restricted peptides (less the respective counts obtained before the treatment), will be considered as a primary indication of the vaccine effectiveness.
ii. Delayed type hypersensitivity (DTH) response to the mix of the melanoma-related peptides, injected intradermally in vivo, and DTH to autologous tumor lysates, in all cases when autologous tumor tissue is available.
iii. Delayed type hypersensitivity (DTH) responses to KLH and PADRE injected intradermally in vivo.
|Study Start Date:||October 2006|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: peptide-pulsed type-1-polarized dendritic cells
intralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1)
|Biological: polarized dendritic cells|
Experimental: peptide-pulsed mature non-polarized dendritic cells (cDCs)
intralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs)
|Biological: non-polarized dendritic cells|
- Compare the safety of intralymphatic autologous type-1-polarized dendritic cell vaccine vs autologous mature dendritic cell vaccine loaded with antigenic peptides and proteins in patients with stage III or IV melanoma.
- Determine peripheral blood CD8+ and CD4+ T-cell responses to HLA-presented melanoma epitopes and autologous tumor cells using interferon gamma and interleukin-5 ELISPOT assay.
- Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients.
- Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients.
- Correlate treatment-associated changes in immune response with clinical outcome.
OUTLINE: This is a randomized, open-label, dose-escalation study. Patients are randomized to 1 of 2 formulations of dendritic cell (DC) vaccines.
- Arm I: Patients receive intralymphatic autologous type-1-polarized (by interleukin-1-beta, tumor necrosis factor [TNF] alfa, interferon alfa, poly-I:C, and interferon gamma) DC vaccine that has been loaded with tumor-related peptide antigens (gp100:209-217[210M] peptide, tyrosinase peptide, MART-1:27-35 peptide, MAGE-3/6, and EphA2) and proteins (keyhole limpet hemocyanin [KLH; first course] or pan-DR epitope [PADRE] [second course]) every 6 hours on days 1-4 of weeks 1 and 6.
- Arm II: Patients receive intralymphatic autologous mature (by interleukin-1-beta, TNF alfa, interleukin-6, and prostaglandin E_2) DC vaccine that has been loaded with tumor-related peptide antigens and proteins as in arm I every 6 hours on days 1-4 of weeks 1 and 6.
Patients achieving complete response receive 2 more courses of treatment (3 months apart). Patients achieving partial response receive up to 10 more courses of treatment (1 month apart) in the absence of disease progression or unacceptable toxicity.
In each arm, cohorts of 4-7 patients receive escalating doses of DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 7 patients experience dose-limiting toxicity.
Blood samples are obtained at baseline and periodically during and after treatment. Samples are examined by immunoenzyme techniques for immunologic measurements.
After completion of study therapy, patients are followed periodically for 10½ years and then annually thereafter.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00390338
|United States, Pennsylvania|
|UPMC Cancer Center at Magee-Womens Hospital|
|Pittsburgh, Pennsylvania, United States, 15213|
|UPMC Cancer Centers|
|Pittsburgh, Pennsylvania, United States, 15232|
|Study Chair:||Ahmad A. Tarhini, MD, MS||University of Pittsburgh|