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

NCT ID: NCT00071981

Last Updated: 2023-06-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-05-09

Study Completion Date

2014-01-31

Brief Summary

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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

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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.

Conditions

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Melanoma (Skin)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type BIOLOGICAL

Given by injection

multi-epitope melanoma peptide vaccine

Intervention Type BIOLOGICAL

Given by injection

sargramostim

Intervention Type BIOLOGICAL

Given by injection

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.

Group Type EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type BIOLOGICAL

Given by injection

multi-epitope melanoma peptide vaccine

Intervention Type BIOLOGICAL

Given by injection

sargramostim

Intervention Type BIOLOGICAL

Given by injection

tetanus peptide melanoma vaccine

Intervention Type BIOLOGICAL

Given by injection

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.

Group Type EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type BIOLOGICAL

Given by injection

melanoma helper peptide vaccine

Intervention Type BIOLOGICAL

Given by injection

multi-epitope melanoma peptide vaccine

Intervention Type BIOLOGICAL

Given by injection

sargramostim

Intervention Type BIOLOGICAL

Given by injection

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.

Group Type EXPERIMENTAL

incomplete Freund's adjuvant

Intervention Type BIOLOGICAL

Given by injection

melanoma helper peptide vaccine

Intervention Type BIOLOGICAL

Given by injection

sargramostim

Intervention Type BIOLOGICAL

Given by injection

Interventions

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incomplete Freund's adjuvant

Given by injection

Intervention Type BIOLOGICAL

melanoma helper peptide vaccine

Given by injection

Intervention Type BIOLOGICAL

multi-epitope melanoma peptide vaccine

Given by injection

Intervention Type BIOLOGICAL

sargramostim

Given by injection

Intervention Type BIOLOGICAL

tetanus peptide melanoma vaccine

Given by injection

Intervention Type BIOLOGICAL

Other Intervention Names

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Montanide ISA-51 6 melanoma helper peptides restricted by class II MHC molecules, restricted by HLADR molecules, 6 class II MHC-Restricted Melanoma-Associated Peptides 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 rhu GM-CSF, Leukine, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Modified Tetanus p2 peptide restricted by class II MHC molecules, Peptide-Tet

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Craig L. Slingluff, MD

Role: STUDY_CHAIR

University of Virginia

Locations

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Veterans Affairs Medical Center - Palo Alto

Palo Alto, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Rush-Copley Cancer Care Center

Aurora, Illinois, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Hematology and Oncology Associates

Chicago, Illinois, United States

Site Status

Midwest Center for Hematology/Oncology

Joliet, Illinois, United States

Site Status

Joliet Oncology-Hematology Associates, Limited - West

Joliet, Illinois, United States

Site Status

North Shore Oncology and Hematology Associates, Limited - Libertyville

Libertyville, Illinois, United States

Site Status

Cancer Care and Hematology Specialists of Chicagoland - Niles

Niles, Illinois, United States

Site Status

Hematology Oncology Associates - Skokie

Skokie, Illinois, United States

Site Status

Carle Cancer Center at Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

William N. Wishard Memorial Hospital

Indianapolis, Indiana, United States

Site Status

Saint Anthony Memorial Health Centers

Michigan City, Indiana, United States

Site Status

McCreery Cancer Center at Ottumwa Regional

Ottumwa, Iowa, United States

Site Status

Greater Baltimore Medical Center Cancer Center

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Union Hospital Cancer Program at Union Hospital

Elkton, Maryland, United States

Site Status

Borgess Medical Center

Kalamazoo, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Site Status

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States

Site Status

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, United States

Site Status

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, United States

Site Status

Ridgeview Medical Center

Waconia, Minnesota, United States

Site Status

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, United States

Site Status

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Site Status

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Site Status

Christ Hospital Cancer Center

Cincinnati, Ohio, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, United States

Site Status

St. Mary Regional Cancer Center

Langhorne, Pennsylvania, United States

Site Status

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Medical X-Ray Center, PC

Sioux Falls, South Dakota, United States

Site Status

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States

Site Status

Center for Cancer Treatment & Prevention at Sacred Heart Hospital

Eau Claire, Wisconsin, United States

Site Status

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, United States

Site Status

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, United States

Site Status

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Saint Joseph's Hospital

Marshfield, Wisconsin, United States

Site Status

Marshfield Clinic - Lakeland Center

Minocqua, Wisconsin, United States

Site Status

Ministry Medical Group at Saint Mary's Hospital

Rhinelander, Wisconsin, United States

Site Status

Marshfield Clinic - Indianhead Center

Rice Lake, Wisconsin, United States

Site Status

Saint Michael's Hospital Cancer Center

Stevens Point, Wisconsin, United States

Site Status

Marshfield Clinic - Wausau Center

Wausau, Wisconsin, United States

Site Status

Marshfield Clinic - Weston Center

Weston, Wisconsin, United States

Site Status

Marshfield Clinic - Wisconsin Rapids Center

Wisconsin Rapids, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

E1602

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000335055

Identifier Type: -

Identifier Source: org_study_id

NCT00464152

Identifier Type: -

Identifier Source: nct_alias

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