Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
- 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
- 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
- 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
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
Ahmad A. Tarhini, MD, MS
University of Pittsburgh
United States: Food and Drug Administration
|UPMC Cancer Center at Magee-Womens Hospital||Pittsburgh, Pennsylvania 15213-3180|
|UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|