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

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: MART-1 antigen; Biological: IL-2; Biological: gp100 antigen; Biological: GM-CSF; Biological: MART-1a peptide

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Time to progression	24 months
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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): January 2, 2013

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimate): May 7, 2007

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 15, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; stage III melanoma; stage II melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Aldesleukin; Interleukin-2
• Other Study ID Numbers: CDR0000542631; P30CA015083 (U.S. NIH Grant/Contract); MC0575 (Other Identifier: Mayo Clinic Cancer Center); 06-002650 (Other Identifier: Mayo Clinic IRB); NCI-2009-1306 (Registry Identifier: NCI-CTRP)