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

Alternate Title

Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	NCI	UVACC-HIC-11491 Mel 44, UVACC-34104, UVACC-MEL-44, UVACC-GCRC-CLS013, UVACC-HITC-02620, MDA-2005-0070, NCT00118274

Objectives

Primary

1. Determine the safety of adjuvant vaccine therapy comprising multi-epitope melanoma peptides (MP) and multi-epitope melanoma helper peptides (MHP) emulsified in Montanide ISA-51 in patients with resected stage IIB-IV melanoma.
2. Determine the safety of administering cyclophosphamide before vaccination in these patients.
3. Compare the magnitude of immune response against vaccination comprising MP in combination with either MHP or tetanus toxoid helper peptide (TET) emulsified in Montanide ISA-51 with vs without cyclophosphamide in these patients.

Secondary

1. Compare the response rate and persistence of immune responses in patients treated with these regimens.
2. Compare the magnitude of immune response against vaccination comprising TET or MHP with vs without cyclophosphamide in these patients.
3. Compare the response rate and persistence of immune response against vaccination comprising TET or MHP with vs without cyclophosphamide in these patients.
4. Determine the delayed-type hypersensitivity response to the peptide components of these vaccines in these patients.
5. Compare, preliminarily, disease-free survival of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed melanoma
  • Cutaneous, mucosal, or primary melanoma
  • Stage IIB-IV disease



• Has undergone surgical resection or stereotactic radiosurgery for malignant melanoma ≥ 1 week but ≤ 6 months ago
  • No clinical or radiological evidence of disease after surgical resection or stereotactic radiosurgery by chest x-ray or CT scan*, abdominal and pelvic CT scan*, and head CT scan or MRI

   [Note: *Positron emission tomography scan/CT fusion scan may replace scans of the chest, abdomen, and pelvis]




• Must have ≥ 2 intact (undissected) axillary and/or inguinal lymph node basins



• HLA-A1, -A2, or -A3 positive AND HLA-DR1, -DR4, -DR11, -DR13, or -DR15 positive



• Ineligible for OR refused interferon



• No ocular melanoma



• Brain metastases allowed provided all of the following criteria are met:
  • No more than 3 total brain metastases
  • Each metastasis ≤ 2 cm in diameter at the time of study entry
  • Each metastasis was completely removed by surgery or treated with stereotactic radiosurgery
  • No evidence of brain metastasis progression since the most recent treatment

Prior/Concurrent Therapy:

Biologic therapy

• No prior vaccination with any of the synthetic peptides used in this study
  • Prior vaccinations (containing agents other than the synthetic peptides used in this study) that resulted in recurrent disease during or after vaccine administration allowed provided the last vaccination was administered more than 12 weeks ago
• More than 4 weeks since prior and no concurrent interferon (e.g., Intron-A®), interleukins (e.g., Proleukin®), or growth factors (e.g., Procrit®, Aranesp®, or Neulasta®)
• More than 4 weeks since prior and no concurrent allergy desensitization injections
• No influenza vaccines for at least 2 weeks before or after study vaccine administration

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy, including nitrosoureas

Endocrine therapy

• More than 4 weeks since prior and no concurrent oral or parenteral corticosteroids
• No prior or concurrent inhaled steroids (e.g., Advair®, Flovent®, or Azmacort®)
• Prior or concurrent topical corticosteroids allowed

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since other prior and no concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 4 weeks since prior and no other concurrent investigational agents
• More than 30 days since prior and no concurrent participation in another clinical study

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 9 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 2.5 times ULN
• Lactic dehydrogenase ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Hepatitis C negative

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Immunologic

• HIV negative
• No known or suspected allergy to any component of the study vaccines
• No autoimmune disorder with visceral involvement
• No prior or active autoimmune disorder requiring cytotoxic or immunosuppressive therapy
• The following immunologic conditions are allowed:
  • Laboratory evidence of autoimmune disease (e.g., positive anti-nuclear antibody titer) without symptoms
  • Clinical evidence of vitiligo
  • Other forms of depigmenting illness
  • Mild arthritis requiring non-steroidal anti-inflammatory drugs

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Weight ≥ 110 lbs
• No uncontrolled diabetes
  • Hemoglobin A1C < 7%
• No medical contraindication or potential problem that would preclude study compliance
• No other malignancy except squamous cell or basal cell skin cancer without known metastasis, carcinoma in situ of the breast (ductal or lobular) or cervix, or other successfully treated cancer without distant metastasis with no evidence of recurrence or metastasis for > 5 years
• No known active addiction to alcohol or drugs
• No recent (within the past year) or ongoing illicit IV drug use

Expected Enrollment

A total of 173 patients will be accrued for this study within 2 years.

Outcomes

Safety if less than 33% of patients experience a dose-limiting toxicity up to week 52

Immunogenicity by Elispot assay up to week 52

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to HLA-type (HLA-A1 positive vs HLA-A2 positive, HLA-A1 negative, or -A3 negative vs HLA-A3 positive, or -A1 negative) and participating center (University of Virginia [UVA] vs non-UVA). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive vaccine comprising multi-epitope melanoma peptides (MP) and tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally (ID) and subcutaneously (SC) on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.



• Arm II: Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine as in arm I.



• Arm III: Patients receive vaccine comprising MP and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 ID and SC on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.



• Arm IV: Patients receive cyclophosphamide as in arm II. Patients then receive vaccine as in arm III.

Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

University of Virginia Cancer Center

Craig Slingluff, MD, Principal investigator		Ph: 434-243-2611; 800-223-9173 Email: cls8h@virginia.edu

Registry Information
Official Title		A Multicenter Trial to Evaluate the Effects of Administration of Cyclophosphamide and Melanoma-Derived Helper Peptides on the Immunogenicity of a Class I MHC-Restricted Peptide-Based Vaccine in Participants with Resected Melanoma
Trial Start Date		2005-03-03
Trial Completion Date		2010-02-01 (estimated)
Registered in ClinicalTrials.gov		NCT00118274
Date Submitted to PDQ		2005-04-29
Information Last Verified		2008-11-06
NCI Grant/Contract Number		CA44579