Melanoma
Conditions
Keywords
melanoma, peptide, vaccine, adjuvant, advanced
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).
Detailed description
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).
Interventions
BIOLOGICAL4-peptide and 12-peptide melanoma vaccines
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).
Sponsors
Craig L Slingluff, Jr
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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, * patients who have undergone IFN-alpha therapy and have experienced tumor progression while on IFN or after completing IFN. * All patients must have: * Karnofsky performance of 80% or higher, * ECOG performance status of 0 or 1, * Ability and willingness to give informed consent. * Laboratory parameters as follows: * HLA-A1, -A2, or -A3 (+), * ANC \> 1000/mm3, and Platelets \> 100,000 and Hgb \> 9, * Hepatic: AST and ALT up to 2.5 x upper limits of normal (ULN), Bilirubin up to 2.5 x ULN, Alkaline phosphatase up to 2.5 x ULN, * Renal: Creatinine up to 1.5 x ULN, * Serology: HIV negative and Hepatitis C negative within 6 months of study entry, * LDH up to 1.5 x ULN. * Age 18 years or older at the time of study entry.
Exclusion criteria
* 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. * Prior melanoma vaccinations will be an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed