Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Diagnostic, Treatment	Temporarily closed	18 and over	NCI	PCI-UPCI-03-118 7089, NCI-7089, PCI-IRB-0409071, NCT00390338

Objectives

Primary

1. 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.

Secondary

1. 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.
2. Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients.
3. Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients.
4. Correlate treatment-associated changes in immune response with clinical outcome.

Entry Criteria

Disease Characteristics:

• Pathologically confirmed stage III or IVA (M1a) melanoma
  • Recurrent and inoperable disease
  • Any tumor thickness and any number of lymph nodes involved
  • Asymptomatic cutaneous and nodal disease allowed
  • Asymptomatic pulmonary metastatic disease (stage IVB, M1b) allowed
• No advanced visceral disease, including any symptomatic visceral organ involvement, or disease associated with increased serum lactic dehydrogenase (stage IVC, M1c)
• Standard curative or palliative measures do not exist or are no longer effective
• Sufficient numbers of monocytes (≥ 20 x 10⁶) must be obtained for the preparation of the vaccine
  • If an insufficient number of cells is obtained on first venipuncture, a second venipuncture may be performed (not exceeding 550 mL of blood within 8 weeks)
• No brain metastases by contrast-enhanced CT scan or MRI
  • Prior brain metastases allowed provided they were successfully treated and patient has been asymptomatic for ≥ 3 months
• HLA-A2 positive

Prior/Concurrent Therapy:

• Recovered from prior surgery
• No radiotherapy, chemotherapy, or immunotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
• No antibiotics within the past 7 days
• No systemic immunosuppressive agents, including steroids, within the past 4 weeks
  • Concurrent maintenance steroids for adrenal insufficiency allowed
• No other concurrent anticancer investigational or commercial agents or therapies

Patient Characteristics:

• ECOG performance status 0-1
• Life expectancy ≥ 6 months
• Granulocyte count ≥ 2,500/mm³
• Lymphocyte count ≥ 1,000/mm³
• Platelet count > 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Gamma-glutamyl transferase ≤ 2.5 times ULN
• Lactic dehydrogenase ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• No active infection
• No sensitivity to drugs that provide local anesthesia
• No pain uncontrolled by oral analgesics, including opiates and opiate analogs
• No active autoimmune disease
• No HIV, hepatitis B, or hepatitis C positivity
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Negative pregnancy test
• No other malignancy except for nonmelanoma skin cancers or carcinoma in situ of the cervix

Expected Enrollment

A total of 40 patients will be accrued for this study.

Outcomes

Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
Cumulative increase in the sum of specific interferon gamma ELISPOTs against melanoma-specific A2-restricted peptides

Peripheral blood CD8+ and CD4+ T-cell response to HLA-presented melanoma epitopes and autologous tumor cells by interferon gamma and interleukin-5 ELISPOT assay
Delayed-type hypersensitivity (DTH) response to treatment
DTH response to autologous tumor lysates
DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE)
Correlation of 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 E₂) 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 8 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.

Trial Contact Information

Trial Lead Organizations

UPMC Cancer Centers

John Kirkwood, MD, Protocol chair		Ph: 412-692-4724

Registry Information
Official Title		Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients with Metastatic Melanoma
Trial Start Date		2006-10-02
Trial Completion Date		2010-11-26 (estimated)
Registered in ClinicalTrials.gov		NCT00390338
Date Submitted to PDQ		2006-08-16
Information Last Verified		2009-07-08
NCI Grant/Contract Number		CA47904

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