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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2012 by Eastern Cooperative Oncology Group.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00071981
First received: November 4, 2003
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Biological: incomplete Freund's adjuvant
Biological: melanoma helper peptide vaccine
Biological: multi-epitope melanoma peptide vaccine
Biological: sargramostim
Biological: tetanus peptide melanoma vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Multi-Epitope Vaccination With Melanoma Peptides For Cytotoxic T Cells And Helper T Cells For Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Cytotoxic T-cell Lymphocytes (CTL) Response Rate [ Time Frame: Immune response was assessed at pre-registrtion, in weeks 1, 3, 5, 7, 8 ] [ Designated as safety issue: No ]
    Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.


Secondary Outcome Measures:
  • Helper T-cells Response to 6MHP [ Time Frame: Immune response was assessed at pre-registration, in weeks 1,3,5,7,8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Immune response was assessed at pre-registration, in weeks 1,3,5,7,8 ] [ Designated as safety issue: No ]
    Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.

  • Objective Response Rate [ Time Frame: Tumor response was assessed in weeks 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 6 months after last vaccination ] [ Designated as safety issue: No ]
    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.

  • Median Overall Survival (OS) [ Time Frame: assessed every 3 month within 2 years and every 6 months betwen 2 and 5 years ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death from any cause.


Enrollment: 175
Study Start Date: March 2005
Estimated Study Completion Date: January 2014
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (12MP)
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.
Biological: incomplete Freund's adjuvant
Given by injection
Other Name: Montanide ISA-51
Biological: multi-epitope melanoma peptide vaccine
Given by injection
Other Names:
  • 12 Melanoma peptides from melanocyte differentiation protein (MDP) and cancer testis antigen (CTA),
  • 12 melanoma peptides restricted by class I MHC molecules,restricted by HLA-A1, A2, or A3 molecules
Biological: sargramostim
Given by injection
Other Names:
  • rhu GM-CSF,
  • Leukine,
  • Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Experimental: Arm II (12MP/Tet)
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.
Biological: incomplete Freund's adjuvant
Given by injection
Other Name: Montanide ISA-51
Biological: multi-epitope melanoma peptide vaccine
Given by injection
Other Names:
  • 12 Melanoma peptides from melanocyte differentiation protein (MDP) and cancer testis antigen (CTA),
  • 12 melanoma peptides restricted by class I MHC molecules,restricted by HLA-A1, A2, or A3 molecules
Biological: sargramostim
Given by injection
Other Names:
  • rhu GM-CSF,
  • Leukine,
  • Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Biological: tetanus peptide melanoma vaccine
Given by injection
Other Names:
  • Modified Tetanus p2 peptide restricted by class II MHC molecules,
  • Peptide-Tet
Experimental: Arm III (12MP/6MHP)
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.
Biological: incomplete Freund's adjuvant
Given by injection
Other Name: Montanide ISA-51
Biological: melanoma helper peptide vaccine
Given by injection
Other Names:
  • 6 melanoma helper peptides restricted by class II MHC molecules, restricted by
  • HLADR molecules,
  • 6 class II MHC-Restricted Melanoma-Associated Peptides
Biological: multi-epitope melanoma peptide vaccine
Given by injection
Other Names:
  • 12 Melanoma peptides from melanocyte differentiation protein (MDP) and cancer testis antigen (CTA),
  • 12 melanoma peptides restricted by class I MHC molecules,restricted by HLA-A1, A2, or A3 molecules
Biological: sargramostim
Given by injection
Other Names:
  • rhu GM-CSF,
  • Leukine,
  • Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Experimental: Arm IV (6MHP)
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.
Biological: incomplete Freund's adjuvant
Given by injection
Other Name: Montanide ISA-51
Biological: melanoma helper peptide vaccine
Given by injection
Other Names:
  • 6 melanoma helper peptides restricted by class II MHC molecules, restricted by
  • HLADR molecules,
  • 6 class II MHC-Restricted Melanoma-Associated Peptides
Biological: sargramostim
Given by injection
Other Names:
  • rhu GM-CSF,
  • Leukine,
  • Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071981

  Hide Study Locations
Locations
United States, California
Veterans Affairs Medical Center - Palo Alto
Palo Alto, California, United States, 94304
Stanford Cancer Center
Stanford, California, United States, 94305-5824
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Illinois
Rush-Copley Cancer Care Center
Aurora, Illinois, United States, 60504
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Hematology and Oncology Associates
Chicago, Illinois, United States, 60611
Joliet Oncology-Hematology Associates, Limited - West
Joliet, Illinois, United States, 60435
Midwest Center for Hematology/Oncology
Joliet, Illinois, United States, 60432
North Shore Oncology and Hematology Associates, Limited - Libertyville
Libertyville, Illinois, United States, 60048
Cancer Care and Hematology Specialists of Chicagoland - Niles
Niles, Illinois, United States, 60714
Hematology Oncology Associates - Skokie
Skokie, Illinois, United States, 60076
Carle Cancer Center at Carle Foundation Hospital
Urbana, Illinois, United States, 61801
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
William N. Wishard Memorial Hospital
Indianapolis, Indiana, United States, 46202
Saint Anthony Memorial Health Centers
Michigan City, Indiana, United States, 46360
United States, Iowa
McCreery Cancer Center at Ottumwa Regional
Ottumwa, Iowa, United States, 52501
United States, Maryland
Greater Baltimore Medical Center Cancer Center
Baltimore, Maryland, United States, 21204
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Michigan
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Borgess Medical Center
Kalamazoo, Michigan, United States, 49001
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States, 55109
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, United States, 55416
United Hospital
Saint Paul, Minnesota, United States, 55102
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, United States, 55379
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
United States, New Jersey
CCOP - Northern New Jersey
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, Ohio
Christ Hospital Cancer Center
Cincinnati, Ohio, United States, 45219
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
Allentown, Pennsylvania, United States, 18105
St. Mary Regional Cancer Center
Langhorne, Pennsylvania, United States, 19047
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, South Dakota
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105
Medical X-Ray Center, PC
Sioux Falls, South Dakota, United States, 57105
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Wisconsin
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
Eau Claire, Wisconsin, United States, 54701
Marshfield Clinic Cancer Care at Regional Cancer Center
Eau Claire, Wisconsin, United States, 54701
Gundersen Lutheran Center for Cancer and Blood
La Crosse, Wisconsin, United States, 54601
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Saint Joseph's Hospital
Marshfield, Wisconsin, United States, 54449
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, United States, 54548
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, United States, 54501
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, United States, 54868
Saint Michael's Hospital Cancer Center
Stevens Point, Wisconsin, United States, 54481
Marshfield Clinic - Wausau Center
Wausau, Wisconsin, United States, 54401
Marshfield Clinic - Weston Center
Weston, Wisconsin, United States, 54476
Marshfield Clinic - Wisconsin Rapids Center
Wisconsin Rapids, Wisconsin, United States, 54494
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Craig L. Slingluff, MD University of Virginia
  More Information

Additional Information:
No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00071981     History of Changes
Obsolete Identifiers: NCT00464152
Other Study ID Numbers: CDR0000335055, U10CA021115, E1602
Study First Received: November 4, 2003
Results First Received: November 24, 2012
Last Updated: November 30, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Freund's Adjuvant
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014