Vaccine Therapy Using Melanoma Peptides for Cytotoxic T Cells and Helper T Cells in Treating Patients With Metastatic Melanoma
- Conditions
- Melanoma (Skin)
- Interventions
- Biological: incomplete Freund's adjuvantBiological: multi-epitope melanoma peptide vaccineBiological: melanoma helper peptide vaccineBiological: sargramostimBiological: tetanus peptide melanoma vaccine
- 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
-
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
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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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (12MP) multi-epitope melanoma peptide vaccine Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) 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 III (12MP/6MHP) multi-epitope melanoma peptide vaccine Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 (6MHP) melanoma helper peptide vaccine Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 I (12MP) incomplete Freund's adjuvant Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) 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 (12MP/Tet) sargramostim Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 (12MP/6MHP) melanoma helper peptide vaccine Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 (6MHP) incomplete Freund's adjuvant Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 II (12MP/Tet) tetanus peptide melanoma vaccine Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 II (12MP/Tet) multi-epitope melanoma peptide vaccine Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 (12MP/6MHP) incomplete Freund's adjuvant Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 (12MP/6MHP) sargramostim Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 (6MHP) sargramostim Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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 I (12MP) sargramostim Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 (incomplete Freund's adjuvant) 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 (12MP/Tet) incomplete Freund's adjuvant Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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.
- 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)
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
UPMC Cancer Centers
🇺🇸Pittsburgh, Pennsylvania, United States
Greater Baltimore Medical Center Cancer Center
🇺🇸Baltimore, Maryland, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Veterans Affairs Medical Center - Palo Alto
🇺🇸Palo Alto, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Hematology and Oncology Associates
🇺🇸Chicago, Illinois, United States
Rush-Copley Cancer Care Center
🇺🇸Aurora, Illinois, United States
Midwest Center for Hematology/Oncology
🇺🇸Joliet, Illinois, United States
Joliet Oncology-Hematology Associates, Limited - West
🇺🇸Joliet, Illinois, United States
North Shore Oncology and Hematology Associates, Limited - Libertyville
🇺🇸Libertyville, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Hematology Oncology Associates - Skokie
🇺🇸Skokie, Illinois, United States
Carle Cancer Center at Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Cancer Care and Hematology Specialists of Chicagoland - Niles
🇺🇸Niles, Illinois, United States
Saint Anthony Memorial Health Centers
🇺🇸Michigan City, Indiana, United States
McCreery Cancer Center at Ottumwa Regional
🇺🇸Ottumwa, Iowa, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Union Hospital Cancer Program at Union Hospital
🇺🇸Elkton, Maryland, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
St. Mary Regional Cancer Center
🇺🇸Langhorne, Pennsylvania, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Medical X-Ray Center, PC
🇺🇸Sioux Falls, South Dakota, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Clinic Cancer Care at Regional Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Gundersen Lutheran Center for Cancer and Blood
🇺🇸La Crosse, Wisconsin, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Marshfield Clinic - Lakeland Center
🇺🇸Minocqua, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States
Marshfield Clinic - Indianhead Center
🇺🇸Rice Lake, Wisconsin, United States
Saint Michael's Hospital Cancer Center
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Clinic - Wausau Center
🇺🇸Wausau, Wisconsin, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸Miami, Florida, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
William N. Wishard Memorial Hospital
🇺🇸Indianapolis, Indiana, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
CCOP - Northern New Jersey
🇺🇸Hackensack, New Jersey, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States