Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	ECOG-E1602 NCT00071981, E1602

Objectives

1. Compare the cytotoxic T-cell response to each of 12 melanoma peptides restricted by HLA-A1, -A2, or -A3 in patients with metastatic melanoma vaccinated with or without these 12 melanoma peptides and with or without helper peptides.
2. Compare the helper T-cell response to each of 6 melanoma helper peptides restricted by HLA-DR molecules in patients treated with these vaccinations.
3. Determine whether the addition of 6 melanoma helper peptides to a vaccine containing multiple class I MHC-restricted peptides augments T-cell responses to the class I restricted peptides in these patients.
4. Determine, preliminarily, whether booster vaccination maintains immune response in patients treated with these vaccinations.
5. Compare the rates of clinical response and survival in patients treated with these vaccinations.
6. Determine, preliminarily, whether cellular immune response correlates with clinical response and survival rates in patients treated with these vaccinations.

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage IV melanoma
  • Multiple primary melanomas allowed
  • Metastasis may be from a cutaneous, mucosal, ocular, or unknown primary site



• Measurable disease by 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



• HLA-A1, -A2, or -A3 positive



• Prior brain metastases allowed provided all of the following are true:
  • No more than 3 brain metastases
  • Metastatic lesions no greater than 2 cm
  • 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

Prior/Concurrent Therapy:

Biologic therapy

• At least 4 weeks since prior sargramostim (GM-CSF), interferon alfa-2b, or interleukin-2
• No prior vaccination with any of the study peptides

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• 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
• No concurrent corticosteroids
• No concurrent topical or systemic steroids

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy to measurable disease
• At least 4 weeks since prior local control or palliative radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior major surgery
• No concurrent surgery

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 4,000/mm³
• Platelet count at least 100,000/mm³
• Lymphocyte count at least 700/mm³

Hepatic

• SGOT and 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

Renal

• Creatinine no greater than 1.8 mg/dL

Immunologic

• No known or suspected major allergy to any components of the study vaccine
• No significant detectable infection
• No immunosuppression conditions
• No prior or active autoimmune disorder requiring cytotoxic or immunosuppressive therapy, except for any of the following:
  • Presence of laboratory evidence of autoimmune disease (e.g., positive ANA titer) without symptoms
  • Clinical evidence of vitiligo or other forms of depigmenting illness
  • Mild arthritis requiring nonsteroidal anti-inflammatory medication
• No autoimmune disorder with visceral involvement

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No recent (within the past year) or concurrent addiction to alcohol or illicit drugs
• 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

Expected Enrollment

A total of 176 patients (44 per treatment arm) will be accrued for this study within 3 years.

Outcomes

Immune response as measured by amount of peripheral blood T-cell lymphocytes present over the first 6 weeks

Clinical response as measured by amount of helper T-cells present at week 8

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 (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.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Craig Slingluff, MD, Protocol chair		Ph: 434-243-2611; 800-223-9173 Email: cls8h@virginia.edu
John Kirkwood, MD, Protocol co-chair		Ph: 412-692-4724

Registry Information
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
Trial Start Date		2005-03-21
Trial Completion Date		2009-03-28
Registered in ClinicalTrials.gov		NCT00071981
Date Submitted to PDQ		2003-09-11
Information Last Verified		2009-03-26
NCI Grant/Contract Number		CA21115

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