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

Alternate Title

Vaccine Therapy and GM-CSF With or Without Low-Dose Aldesleukin in Treating Patients With Stage II, Stage III, or Stage IV Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Treatment Temporarily closed 18 and over NCI MAYO-MC0575 MC0575, NCT00470015

Objectives

1. Determine the safety and toxicity profile of peptide vaccine comprising MART-1 antigen, gp100 antigen, and survivin antigen in combination with sargramostim (GM-CSF) emulsified in incomplete Freund's adjuvant (IFA) with or without low-dose aldesleukin in patients with stage II-IV melanoma.
2. Determine the immunologic effects of two different doses of GM-CSF coemulsified with melanoma peptides in IFA in these patients.
3. Determine the immunological effects of low-dose aldesleukin therapy administered after peptide immunization in these patients.
4. Collect preliminary data on the impact of the vaccine on clinical outcomes in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed melanoma
  • Stage II-IV disease



• Completely resected disease



• No known standard therapy that is potentially curative or proven capable of extending life expectancy exists



• HLA-A2 positive

Prior/Concurrent Therapy:

• No chemotherapy within the past 4 weeks and recovered
• No biologic therapy within the past 4 weeks
• No radiation therapy within the past 4 weeks

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/mm³
• Hemoglobin > 10 g/dL
• Platelet count ≥ 50,000/mm³
• AST ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled or current infection
• No known allergy to vaccine or immunoadjuvant components
• No known immune deficiency

Expected Enrollment

A total of 20 patients will be accrued for this study.

Outcomes

Percent changes in peptide vaccine-specific immune responses (tetramer frequencies) from pretreatment levels
Number and severity of hematologic and nonhematologic toxicities observed at each dose level

Delayed-type hypersensitivity positivity
Maximum percent change in CD4, CD8, CD14, CD19, and C20 levels from preimmunization levels
Time to treatment failure
Time to progression

Outline

This is a pilot study. Patients are stratified according to disease stage (II vs III or IV). Patients are sequentially enrolled into 1 of 4 different dose schedules.

• Dose schedule 1: Patients receive gp100 antigen, MART-1 antigen, survivin antigen, and sargramostim (GM-CSF) emulsified in incomplete Freund's adjuvant (peptide vaccine) subcutaneously (SC) on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.



• Dose schedule 2: Patients receive peptide vaccine as in group 1. Patients also receive low-dose aldesleukin SC twice daily on days 7-20. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.



• Dose schedule 3: Patients receive peptide vaccine as in group 1 except with a higher dose of GM-CSF. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.



• Dose schedule 4: Patients receive peptide vaccine as in group 1 except with a higher dose of GM-CSF. Patients also receive low-dose aldesleukin SC twice daily on days 7-20. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 5 patients receive treatment at subsequent dose schedule until the maximum tolerated dose schedule (MTDS) is determined. The MTDS is defined as the dose schedule preceding that at which 2 of 5 patients experience dose-limiting toxicity within the first course.

After completion of study therapy, patients are followed every 3 months for up to 2 years.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Svetomir Markovic, MD, PhD, Protocol chair		Ph: 507-284-3903
Mark Pittelkow, MD, Protocol co-chair		Ph: 507-284-7821 Email: pittelkow.mark@mayo.edu
Ravi Rao, MD, MBBS, Protocol co-chair		Ph: 507-284-2511
Edward Creagan, MD, Protocol co-chair		Ph: 507-284-8413
Judith Kaur, MD, Protocol co-chair		Ph: 507-266-5365 Email: kaur.judith@mayo.edu
Lori Erickson, MD, Protocol co-chair		Ph: 507-284-1199
Henry Pitot, MD, Protocol co-chair		Ph: 507-284-2511 Email: pitot.henry@mayo.edu

Registry Information
Official Title		Melanoma Peptide Vaccines (MART1 Analog, gp100 and Survivin) with GM-CSF and Low-Dose IL-2 as Immune Adjuvants, A Pilot Study
Trial Start Date		2007-02-23
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00470015
Date Submitted to PDQ		2007-03-29
Information Last Verified		2008-03-30
NCI Grant/Contract Number		CA15083