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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Melanoma (Skin)

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Cytotoxic T-cell Lymphocytes (CTL) Response Rate

Outcome Description:

Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.

Outcome Time Frame:

Immune response was assessed at pre-registrtion, in weeks 1, 3, 5, 7, 8

Safety Issue:

No

Principal Investigator

Craig L. Slingluff, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Virginia

Authority:

United States: Federal Government

Study ID:

CDR0000335055

NCT ID:

NCT00071981

Start Date:

March 2005

Completion Date:

January 2014

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma

Name

Location

Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Carle Cancer CenterUrbana, Illinois  61801
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
CCOP - Northern New JerseyHackensack, New Jersey  07601
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Joliet Oncology-Hematology Associates, Limited - WestJoliet, Illinois  60435
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Saint Anthony Memorial Health CentersMichigan City, Indiana  46360
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Avera Cancer InstituteSioux Falls, South Dakota  57105
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Marshfield Clinic - Indianhead CenterRice Lake, Wisconsin  54868
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Veterans Affairs Medical Center - Palo AltoPalo Alto, California  94304
McCreery Cancer Center at Ottumwa RegionalOttumwa, Iowa  52501
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Hematology Oncology Associates - SkokieSkokie, Illinois  60076
UPMC Cancer CentersPittsburgh, Pennsylvania  15232
Hematology and Oncology AssociatesChicago, Illinois  60611
Midwest Center for Hematology/OncologyJoliet, Illinois  60432
North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyville, Illinois  60048
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
St. Mary Regional Cancer CenterLanghorne, Pennsylvania  19047
Stanford Cancer CenterStanford, California  94305-5824
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Cancer Care and Hematology Specialists of Chicagoland - NilesNiles, Illinois  60714
William N. Wishard Memorial HospitalIndianapolis, Indiana  46202
Greater Baltimore Medical Center Cancer CenterBaltimore, Maryland  21204
Union Hospital Cancer Program at Union HospitalElkton MD, Maryland  21921
Christ Hospital Cancer CenterCincinnati, Ohio  45219
Center for Cancer Treatment & Prevention at Sacred Heart HospitalEau Claire, Wisconsin  54701
Marshfield Clinic Cancer Care at Regional Cancer CenterEau Claire, Wisconsin  54701
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Marshfield Clinic - Lakeland CenterMinocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's HospitalRhinelander, Wisconsin  54501
Saint Michael's Hospital Cancer CenterStevens Point, Wisconsin  54481
Marshfield Clinic - Wausau CenterWausau, Wisconsin  54401
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids CenterWisconsin Rapids, Wisconsin  54494