Vaccine Therapy Using Melanoma Peptides for Cytotoxic T Cells and Helper T Cells in Treating Patients With Metastatic Melanoma

Phase 2

Completed

Conditions: Melanoma (Skin)

Registration Number: NCT00071981

Lead Sponsor: Eastern Cooperative Oncology Group

Brief Summary: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.

PURPOSE: This randomized phase II trial is studying four different vaccines using melanoma peptides from cytotoxic T cells and helper T cells to see how well they work in treating patients with metastatic melanoma.

Detailed Description: OBJECTIVES:

* Compare the cytotoxic T-cell response to each of 12 melanoma peptides restricted by Human Leukocyte Antigen (HLA)-A1, -A2, or -A3 in patients with metastatic melanoma vaccinated with or without these 12 melanoma peptides and with or without helper peptides.

* Compare the helper T-cell response to each of 6 melanoma helper peptides restricted by HLA-DR molecules in patients treated with these vaccinations.

* Determine whether the addition of 6 melanoma helper peptides to a vaccine containing multiple class I Major histocompatibility complex (MHC)-restricted peptides augments T-cell responses to the class I restricted peptides in these patients.

* Determine, preliminarily, whether booster vaccination maintains immune response in patients treated with these vaccinations.

* Compare the rates of clinical response and survival in patients treated with these vaccinations.

* Determine, preliminarily, whether cellular immune response correlates with clinical response and survival rates in patients treated with these vaccinations.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to HLA type (HLA-A1 vs HLA-A2 vs HLA-A1 and -A2 vs HLA-A3) and planned sentinel immunized node biopsy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (Granulocyte-macrophage colony-stimulating factor, GM-CSF) and Montanide ISA-51 or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.

* Arm II: Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 1 tetanus helper peptide emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.

* Arm III (closed to accrual as of 5/19/08): Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.

* Arm IV: Patients receive 2 injections of multi-epitope peptide vaccine comprising 6HP emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.

In all arms, patients continue therapy in the absence of unacceptable toxicity or disease progression necessitating other urgent therapy.

Patients are evaluated at 8 and 12 weeks. Beginning 2-3 weeks after the week-12 evaluation, patients with no evidence of disease progression may receive booster vaccinations according to their randomized treatment arm. Patients receive booster vaccination ID and SC once weekly for 3 weeks. Treatment repeats every 9 weeks for 1 course, every 12 weeks for 2 courses, and then every 24 weeks for 2 courses OR for up to 2 years (whichever comes first) provided the patient does not require an urgent change in therapy.

After completion of study treatment, patients are followed every 6 months for 2 years and then for survival for 5 years from study randomization.

ACTUAL ACCRUAL: A total of 175 patients were accrued for this study during March 2005 and January 2009.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 175

Inclusion Criteria

Histologically confirmed stage IV melanoma
- Multiple primary melanomas allowed
- Metastasis may be from a cutaneous, mucosal, ocular, or unknown primary site
Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST criteria)
Must have 2 extremities uninvolved with tumor
Must have at least 2 intact (undissected) axillary and/or inguinal lymph node basins
- Prior sentinel node biopsy may not have violated the integrity of a nodal basin
  - This extremity may still be considered for vaccination
Human Lymphocyte Antigen (HLA)-A1, -A2, or -A3 positive
Prior brain metastases allowed provided all of the following are true:
- Surgically resected or treated with gamma-knife or stereotactic radiosurgery
- No disease progression in the brain for the past 3 months
- More than 30 days since prior steroids for the management of brain metastases
Age: 18 and over
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Adequate organ function measured within 4 weeks before randomization:
- White blood cell (WBC) at least 4,000/mm^3
- Platelet count at least 100,000/mm^3
- Lymphocyte count at least 700/mm^3
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) no greater than 2 times upper limit of normal (ULN)
- Bilirubin no greater than 2 times ULN
- Alkaline phosphatase no greater than 2 times ULN
- Lactic dehydrogenase no greater than 2 times ULN
- Creatinine no greater than 1.8 mg/dL
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 5 years except nonmetastatic squamous cell or basal cell skin cancer, ductal or lobular carcinoma in situ of the breast, or carcinoma in situ of the cervix
At least 4 weeks since prior sargramostim (GM-CSF), interferon alfa-2b, or interleukin-2
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
More than 30 days since prior systemic corticosteroids, including any of the following:
- Therapeutic doses of oral steroids (e.g., prednisone or dexamethasone)
- Steroid inhalers (e.g., Advair)
  - Topical steroids and nasal steroids with low systemic absorption (e.g., fluticasone) or steroids with low systemic absorption (e.g., triamcinolone hexacetonide) injected into a joint space allowed
At least 4 weeks since prior local control or palliative radiotherapy and recovered
Recovered from prior major surgery

Exclusion criteria:

More than 3 brain metastases
Metastatic lesions greater than 2 cm
Concurrent radiotherapy
Prior radiotherapy to measurable disease
Concurrent surgery
Concurrent corticosteroids
Concurrent topical or systemic steroids
Concurrent chemotherapy
Prior vaccination with any of the study peptides
Recent (within the past year) or concurrent addiction to alcohol or illicit drugs
Pregnant or nursing
Known or suspected major allergy to any components of the study vaccine
Significant detectable infection
Immunosuppression conditions
Prior or active autoimmune disorder requiring cytotoxic or mmunosuppressive therapy, except for any of the following:
- Presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody (ANA) titer) without symptoms
- Clinical evidence of vitiligo or other forms of depigmenting illness
- Mild arthritis requiring nonsteroidal anti-inflammatory medication
Autoimmune disorder with visceral involvement

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Cytotoxic T-cell Lymphocytes (CTL) Response Rate	Immune response was assessed at pre-registrtion, in weeks 1, 3, 5, 7, 8	Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.

Secondary Outcome Measures

Name	Time	Method
Helper T-cells Response to 6MHP	Immune response was assessed at pre-registration, in weeks 1,3,5,7,8	Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.
Helper T Cell Response to Tetanus	Immune response was assessed at pre-registration, in weeks 1,3,5,7,8	Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.
Median Overall Survival (OS)	assessed every 3 month within 2 years and every 6 months betwen 2 and 5 years	OS was defined as the time from registration to death from any cause.
Objective Response Rate	Tumor response was assessed in weeks 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 6 months after last vaccination	Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate is calculated as the number of patients with complete response (disappearance of all lesions) or partial response () divided by total number of evaluable patients.

Trial Locations

Locations (65): Veterans Affairs Medical Center - Palo Alto
🇺🇸
Palo Alto, California, United States
Stanford Cancer Center
🇺🇸
Stanford, California, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
CCOP - Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
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Miami, Florida, United States
Rush-Copley Cancer Care Center
🇺🇸
Aurora, Illinois, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
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Chicago, Illinois, United States
Hematology and Oncology Associates
🇺🇸
Chicago, Illinois, United States
Midwest Center for Hematology/Oncology
🇺🇸
Joliet, Illinois, United States
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Veterans Affairs Medical Center - Palo Alto
🇺🇸Palo Alto, California, United States