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

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00071981
• Other study ID #: CDR0000335055
• Secondary ID: U10CA021115E1602
• Status: Completed
• Phase: Phase 2
• Start date: May 9, 2005
• Est. completion date: January 2014

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00464152

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: January 2014
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• incomplete Freund's adjuvant
Given by injection
• melanoma helper peptide vaccine
Given by injection
• multi-epitope melanoma peptide vaccine
Given by injection
• sargramostim
Given by injection
• tetanus peptide melanoma vaccine
Given by injection

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Christ Hospital Cancer Center	Cincinnati	Ohio
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
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	Fairview Southdale Hospital	Edina	Minnesota
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Midwest Center for Hematology/Oncology	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	St. Mary Regional Cancer Center	Langhorne	Pennsylvania
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
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	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Stanford Cancer Center	Stanford	California
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
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	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cytotoxic T-cell Lymphocytes (CTL) Response Rate	Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.	Immune response was assessed at pre-registrtion, in weeks 1, 3, 5, 7, 8
Secondary	Helper T-cells Response to 6MHP	Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.	Immune response was assessed at pre-registration, in weeks 1,3,5,7,8
Secondary	Helper T Cell Response to Tetanus	Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.	Immune response was assessed at pre-registration, in weeks 1,3,5,7,8
Secondary	Objective Response Rate	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.	Tumor response was assessed in weeks 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 6 months after last vaccination
Secondary	Median Overall Survival (OS)	OS was defined as the time from registration to death from any cause.	assessed every 3 month within 2 years and every 6 months betwen 2 and 5 years