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

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00470015
• Other study ID #: CDR0000542631
• Secondary ID: P30CA015083MC057
• Status: Completed
• Phase: Phase 1
• Start date: March 2007
• Est. completion date: January 2, 2013

Study information

• Verified date: February 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2, 2013
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• MART-1 antigen
1000 mcg; Day 1 of a 21 day cycle x 4
• IL-2
0.5x10^6/m^2
• gp100 antigen
1000 mcg; Day 1 of a 21 day cycle x 4
• GM-CSF
300mcg
• MART-1a peptide
1000 mcg; Day 1 of a 21 day cycle x 4

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent changes in peptide vaccine-specific immune responses (tetramer frequencies) from pretreatment levels		12 weeks
Primary	Number and severity of hematologic and nonhematologic toxicities observed at each dose level		12 weeks
Secondary	Delayed-type hypersensitivity positivity		12 weeks
Secondary	Maximum percent change in CD4, CD8, CD14, CD19, and C20 levels from preimmunization levels		12 weeks
Secondary	Time to treatment failure		12 weeks
Secondary	Time to progression		24 months