Evaluation of the Immunogenicity of Vaccination With Multiple Synthetic Melanoma Peptides With Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)-In-Adjuvant, in Patients With Advanced Melanoma

NCT00938223 | Completed Phase 2

• 1 other identifier: 8878
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase II study of a vaccine comprising melanoma peptides and a tetanus helper peptide, administered in GM-CSF-in-adjuvant. Patients will be randomized to receive one of two different vaccine regimens. Patients will be stratified by stage of disease (IIB versus III versus IV).

Conditions

Melanoma

Keywords

melanoma; peptide; vaccine; adjuvant; advanced

Outcome Measures

Primary Outcomes (1)

• Safety of the 12-peptide mixture and cumulative number of T cells derived from the sentinel immunized node that are reactive to the 12 melanoma peptides included in the vaccine, in the context of HLA-A1, -A2, or -A3.

  24 months

Secondary Outcomes (2)

• Immunogenicity of the individual peptides incorporated into the vaccine, cytotoxic and proliferative responses of T-cells to autologous and allogeneic melanoma cells.

  Week 4

• Disease-free survival of stage IIB and stage III patients

  ongoing

Study Arms (2)

4-peptide vaccine

ACTIVE COMPARATOR

Group A will receive 4 class I MHC-restricted synthetic melanoma peptides (1 each restricted by HLA-A1, -A3, and two restricted by HLA-A 2) and a tetanus helper peptide.

Biological: 4-peptide and 12-peptide melanoma vaccines

12-peptide vaccine

ACTIVE COMPARATOR

Group B will receive the 12 class I MHC-restricted synthetic melanoma peptides (4 each restricted to HLA-A1, -A2, and -A3) and a tetanus helper peptide.

Biological: 4-peptide and 12-peptide melanoma vaccines

Interventions

4-peptide and 12-peptide melanoma vaccines BIOLOGICAL

Each vaccination will be administered over a 6-week period (days 1, 8, 15, 29, 36, 43). Patients will be randomized into one of two groups, Group A or Group B. Group A will receive 4 class I MHC-restricted synthetic melanoma peptides (1 each restricted by HLA-A1, -A3, and two restricted by HLA-A2) and a tetanus helper peptide. Group B will receive the 12 class I MHC-restricted synthetic melanoma peptides (4 each restricted to HLA-A1, -A2, and -A3) and a tetanus helper peptide. All vaccines will contain GM-CSF-in-adjuvant and will be administered intradermally and subcutaneously. Concurrent with the first three of these vaccinations, each patient will also receive an additional set of 3 identical vaccinations in a distal site, the response to which will be evaluated at the draining lymph node. This node will be harvested using lymphatic mapping and sentinel node biopsy methods and will be referred to as the sentinel immunized node (SIN).

Also known as: MELITAC 4.1, MELITAC 12.1

12-peptide vaccine; 4-peptide vaccine

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have been diagnosed, by cytologic or histologic examination, with resected AJCC stage IIB, stage III, or stage IV cutaneous or mucosal melanoma.
• Patients who have had brain metastases will be eligible if (a) they have been resected surgically, or (b) there have been 1-3 brain metastases less than or equal to 2 cm that have been treated with the gamma-knife or stereotactic radiosurgery. Surgical resections or gamma-knife must have been completed no greater than 10 months prior to study entry.
• Tumor must express either gp100 (for patients HLA-A2+ or HLA-A3+) or tyrosinase (for patients HLA-A1+ or HLA-A2+) by immunohistochemistry. The tumor deposit(s) to be examined will be the primary lesion for stage IIB patients, or the most recently resected metastatic disease in stage III or stage IV patients. If the most recently resected deposit is not available than material from prior resected tumor will be evaluated.
• Patients who refuse treatment with IFN-alpha despite being candidates for IFN-alpha.
• Patients who are not eligible for treatment with IFN-alpha for the following reasons:
• active ischemic heart disease or cerebro-vascular disease,
• anginal syndrome requiring ongoing medications, or history of myocardial infarction, or arrhythmia disorder,
• history of treatment for depression or active depression, or other psychiatric disorder,
• patients with autoimmune disorders who are not excluded based on criteria listed in section 5.2.8 of the present study,
• patients in whom greater than 6 months have elapsed since their definitive surgical therapy,
• hypersensitivity to IFN-alpha or any component associated with the treatment,
• debilitating medical conditions such as severe pulmonary disease or severe diabetes mellitus,
• patients with thyroid abnormalities whose thyroid function cannot be maintained in the normal range without medication
• patients with resected stage IV disease provided they meet the eligibility criteria for the proposed study,
• patients who discontinue IFN-alpha therapy due to the occurrence of a major toxicity that has been documented by their treating physician,

You may not qualify if:

• Patients with ocular melanoma.
• Patients who are currently receiving cytotoxic chemotherapy, interferon, or radiation or who have received this therapy within the preceding 4 weeks.
• Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 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 childbearing potential must have a negative pregnancy test (urinary or serum beta-HCG) prior to administration of the first vaccine dose. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. This is consistent with existing standards of practice for vaccine and chemotherapy protocols.
• 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 who have systemic autoimmune disease with visceral involvement.
• Patients who have another cancer diagnosis, except that the following diagnoses will be allowed: squamous cell cancer of the skin without known metastasis, basal cell cancer of the skin without known metastasis, carcinoma in situ of the breast (DCIS or LCIS), carcinoma in situ of the cervix, any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 5 years.
• Patients with known addiction to alcohol or drugs who is actively taking those agents, or patients with recent (within 1 year) or ongoing illicit IV drug use.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery; Director of the Human Immune Therapy Center

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: July 13, 2009
• Study Start: August 1, 2000
• Primary Completion: November 1, 2003
• Last Updated: May 2, 2018

Record last verified: 2018-04

Locations

US (1)