Clinical trial NCT00912574: Evaluation of the Effects of Local Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Adjuvant Administration on Dendritic Cells in Skin of Melanoma Patients and in Sentinel Lymph Nodes: MEL38
Official title: Evaluation of the Effects of Local GM-CSF-in-Adjuvant Administration on Dendritic Cells in Skin of Melanoma Patients and in Sentinel Lymph Nodes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Melanoma
Keywords: Melanoma
adjuvant
dendritic cells
vaccine
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2009-06-03
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Goal: To characterize the cellular events that occur in vivo after vaccination with an emulsion of GMCSF-in-adjuvant.

Design: Open-label, single dose study in two stages.

Detailed description: Regimen: Each injection will be administered to patients with clinical stage I or II melanoma, who have had complete excision of a primary melanoma, but prior to wide excision with or without sentinel node biopsy as definitive surgical therapy.

In Stage 1: Patients will be injected with a 1 ml emulsion containing GM-CSF in saline plus Montanide ISA-51 adjuvant, in skin adjacent to a melanoma biopsy scar.

In Stage 2: Patients will be randomized to receive an injection of one of the following in skin adjacent to the melanoma biopsy scar:

1. 1 ml saline
2. GM-CSF in 1 ml saline
3. an emulsion of Montanide ISA-51 adjuvant and saline
4. an emulsion of GM-CSF in saline plus ml Montanide ISA-51 adjuvant. All vaccines will be administered intradermally. After the injection, each patient will undergo wide excision of the melanoma site, with or without sentinel node biopsy, as clinically indicated.

Eligibility criteria: Inclusion Criteria:

* Patients who have been diagnosed, by histologic and clinical examination, with resected AJCC stage I or II melanoma.
* Patients who have any evidence of metastasis will not be eligible.
* All patients must have:

  1. Karnofsky performance of 80% or higher
  2. ECOG performance status of 0 or 1
  3. Ability and willingness to give informed consent
* Laboratory parameters as follows:

  1. ANC: 90% of lower limit of normal (LLN) to 120% of upper limit of normal (ULN)
  2. Platelets: 100-500 x 103/uL
  3. Hgb: 90% LLN to 120% ULN
  4. Hepatic:

     1. AST, ALT, Bilirubin, and Alk phos within normal limits,
     2. LDH up to 1.2 x ULN
  5. Renal:

     1. Creatinine up to 1.5 x ULN
* Age 18-85 years at the time of study entry.

Exclusion Criteria:

* Patients who are currently receiving cytotoxic chemotherapy, interferon, or radiation or who have received this therapy within the preceding 12 weeks.
* Patients with known or suspected allergies to any component of the vaccine.
* Patients receiving the following medications at study entry or within the preceding 4 weeks are excluded:

  * Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents),
  * Allergy desensitization injections,
  * Corticosteroids, administered parenterally or orally. Topical corticosteroids are acceptable.
  * Any growth factors, Interleukin-2 or other interleukins.
* Pregnancy or the possibility of becoming pregnant during vaccine administration. Female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-HCG) prior to administration of the injection.
* Patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator.
* Patients classified according to the New York Heart Association classification as having Class III or IV heart disease.
* Patients with serious symptomatic active pulmonary disease, with pleural effusions, or with a history of pulmonary edema.
* Patients who have systemic autoimmune disease with visceral involvement.
* Patients with clinically apparent skin infection or other clinically evident inflammation involving the skin adjacent to the melanoma biopsy scar.

Primary outcomes:
measure: Number of dendritic cells (total and mature) accumulating in the dermis after administration of the adjuvant
measure: Proportion of the sentinel node occupied by dendritic cells (total and mature)
Secondary outcomes:
measure: Time to maximal dendritic cell infiltration into the dermis
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Craig L Slingluff, MD
role: PRINCIPAL_INVESTIGATOR
References: