Vaccine Therapy and Interleukin-12 With Either Alum or Sargramostim After Surgery in Treating Patients With Melanoma

Sponsor

University of Southern California (Other)

Overall Status

Completed

CT.gov ID

NCT00031733

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from peptides may make the body build an immune response. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma Melanoma (Skin)	Biological: MART-1 antigen Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: recombinant interleukin-12 Biological: sargramostim Biological: tyrosinase peptide Drug: alum adjuvant Procedure: adjuvant therapy	Phase 2

Detailed Description

OBJECTIVES:

Compare the immune reactivity in patients with resected stage IIB, IIC, III, or IV melanoma vaccinated with tyrosinase, gp100, and MART-1 peptides emulsified with Montanide ISA-51 with interleukin-12 and either alum adjuvant or sargramostim (GM-CSF).

OUTLINE: This is a randomized study. Patients are stratified according to disease stage (cutaneous stage IIB, IIC, III, and IV vs ocular and mucosal stage III and IV). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive vaccine with tyrosinase:368-376 (370D)/gp100:209-217 (210M)/MART-1:26-27 (27L) peptides emulsified with Montanide ISA-51 (ISA-51), low-dose interleukin-12 (IL-12) subcutaneously (SC), and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
Arm II: Patients receive peptide vaccine emulsified with ISA-51, high-dose IL-12 SC, and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.
Arm III: Patients receive peptide vaccine emulsified with ISA-51 on day 1 and low-dose IL-12 SC and sargramostim (GM-CSF) SC on days 1-5 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (20 per treatment arm) will be accrued for this study within 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase II Randomized Trial of a Vaccine Combining Tyrosinase/GP100/MART-1 Peptides Emulsified With Montanide ISA 51 With Interleukin-12 With Alum or GM-CSF for Patients With Resected Stages IIB/C, III and IV Melanoma

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Dec 1, 2004

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of stage IIB, IIC, III, or IV cutaneous melanoma OR stage III or IV ocular or mucosal melanoma
Resected or rendered disease-free
HLA-A2.1-positive by standard cytotoxicity assay
Tumor tissue must be available for analysis of gp100 staining and tyrosinase and MART-1 expression by immunohistochemistry
Must be positive for at least 1 antigen
Failed, ineligible for, or refused prior interferon alfa

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9.0 g/dL
No bleeding disorder

Hepatic:

Bilirubin no greater than 2.0 mg/dL
SGOT/SGPT no greater than 2.5 times normal
No coagulation disorder
Hepatitis surface antigen B negative
Hepatitis C negative

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

No major cardiovascular illness

Pulmonary:

No major respiratory illness

Immunologic:

No prior uveitis
No prior autoimmune inflammatory eye disease
No immune hemolytic anemia
No other active autoimmune disease

Other:

HIV negative
No major gastrointestinal illness
No other malignancy within the past 5 years except squamous cell skin cancer or carcinoma in situ of the cervix curatively treated at least 30 days ago
No major systemic infection (e.g., pneumonia or sepsis)
No other major medical illness
No prior allergic reaction to Montanide ISA-51 or alum adjuvant
No requirement for steroid therapy
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception