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Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma

Phase 1
18 Years
Not Enrolling
Melanoma (Skin)

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Trial Information

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
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.

Inclusion Criteria


- 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 symptomatic visceral disease, including any symptomatic visceral organ
involvement, or disease associated with increased serum lactic dehydrogenase > 2.5
times upper limit of normal (stage IVC, M1c)

- Standard curative or palliative measures do not exist or are no longer effective

- Sufficient numbers of monocytes (≥ 20 x 10^6) 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


- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- Granulocyte count ≥ 1,500/mm³

- Lymphocyte count ≥ 500/mm³

- Platelet count > 70,000/mm³ (for venipuncture/pheresis procedure)

- 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, or other malignancy for which the patient has been continuously disease-free
for ≥ 2 years


- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine

Safety Issue:


Principal Investigator

Ahmad A. Tarhini, MD, MS

Investigator Role:

Study Chair

Investigator Affiliation:

University of Pittsburgh


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • recurrent melanoma
  • stage IV melanoma
  • stage IIIA melanoma
  • stage IIIB melanoma
  • stage IIIC melanoma
  • Melanoma



UPMC Cancer Center at Magee-Womens HospitalPittsburgh, Pennsylvania  15213-3180
UPMC Cancer CentersPittsburgh, Pennsylvania  15232