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

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00470015

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

70.1

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Giving vaccine and different doses of GM-CSF mixed in incomplete Freund's adjuvant, with or without aldesleukin, may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and how well giving vaccine therapy together with GM-CSF, with or without low-dose aldesleukin, works in treating patients with stage II, stage III, or stage IV melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: MART-1 antigen Biological: IL-2 Biological: gp100 antigen Biological: GM-CSF Biological: MART-1a peptide	Phase 1

Detailed Description

OBJECTIVES:

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.
Determine the immunologic effects of two different doses of GM-CSF coemulsified with melanoma peptides in IFA in these patients.
Determine the immunological effects of low-dose aldesleukin therapy administered after peptide immunization in these patients.
Collect preliminary data on the impact of the vaccine on clinical outcomes in these patients.

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Melanoma Peptide Vaccines (MART1 Analog, gp100 and Survivin) With GM-CSF and Low-Dose IL-2 as Immune Adjuvants, A Pilot Study

Actual Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

Jan 2, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MART1 Analog, gp100 and Survivin	Biological: MART-1 antigen 1000 mcg; Day 1 of a 21 day cycle x 4 Biological: IL-2 0.5x10^6/m^2 Other Names: Interleukin-2, Proleukin®, aldesleukin Biological: gp100 antigen 1000 mcg; Day 1 of a 21 day cycle x 4 Biological: GM-CSF 300mcg Other Names: Leukine-Liquid, sargramostatin Biological: MART-1a peptide 1000 mcg; Day 1 of a 21 day cycle x 4

Arm

Intervention/Treatment

Experimental: MART1 Analog, gp100 and Survivin

Biological: MART-1 antigen

1000 mcg; Day 1 of a 21 day cycle x 4

Biological: IL-2

0.5x10^6/m^2

Other Names:

Interleukin-2, Proleukin®, aldesleukin

Biological: gp100 antigen

1000 mcg; Day 1 of a 21 day cycle x 4

Biological: GM-CSF

300mcg

Other Names:

Leukine-Liquid, sargramostatin

Biological: MART-1a peptide

1000 mcg; Day 1 of a 21 day cycle x 4

Outcome Measures

Primary Outcome Measures

Percent changes in peptide vaccine-specific immune responses (tetramer frequencies) from pretreatment levels [12 weeks]
Number and severity of hematologic and nonhematologic toxicities observed at each dose level [12 weeks]

Secondary Outcome Measures

Delayed-type hypersensitivity positivity [12 weeks]
Maximum percent change in CD4, CD8, CD14, CD19, and C20 levels from preimmunization levels [12 weeks]
Time to treatment failure [12 weeks]
Time to progression [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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