Novel Adjuvants for Peptide-Based Melanoma Vaccines

Sponsor

University of Southern California (Other)

Overall Status

Completed

CT.gov ID

NCT00028431

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study to determine the efficacy of a melanoma vaccine chemotherapy cocktail composed of CTLA-4 antibody; tyrosinase, gp100, and MART-1 peptides; and incomplete Freund's adjuvant (IFA) with or without interleukin-12 in patients with resected stage III or IV melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: MDX-CTLA4 Antibody; Tyrosinase/gp100/MART-1 Peptides Melanoma Vaccine	Phase 1

Detailed Description

In the Phase I/II trial, patients with resected stages III and IV melanoma who have been rendered free of disease, but are at high risk of relapse, are treated with peptides/IFA at a dose of 0.5 mg each peptide plus CTLA-4 antibody given intravenously, 3 mg/kg, after each vaccination. In the Phase II randomized study, patients are treated with the melanoma peptide vaccine alone, with CTLA-4 antibody, or with CTLA-4 antibody combined with IL-12 at 30 ng/kg with alum. The peptides are tyrosinase 368-376 (370D); gp100 209-217 (210M); and MART-1 26-35 (27L) which are emulsified with IFA. The dosing schedule for both trials are at 1, 2, 3, 4, 5, and 6 months; then at 9 and 12 for a total of 8 vaccinations.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label Study of MDX-CTLA4 in Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 in the Treatment of Patients With Resected Stage III or IV Melanoma

Study Start Date :

Aug 1, 2001

Actual Primary Completion Date :

Jan 1, 2003

Actual Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Diagnosis of stage III or IV cutaneous, mucosal, or ocular melanoma
Completely resected disease or disease-free
HLA-A2.1 positive
Tumor tissue available for immunohistochemical analysis and staining positive for at least 1 of the specified antigens
At least 1 month since prior therapy for cancer, including radiotherapy and adjuvant therapy
WBC count at least 3,000/mm3
Granulocyte count at least 1,500/mm3
Platelet count at least 100,000/mm3
Hemoglobin at least 9.0 gm/dL
Creatinine no greater than 2.0 mg/dL
Bilirubin no greater than 2.0 mg/dL
SGOT/SGPT no greater than 2.5 times upper limit of normal
ECOG performance status 0-1
Have failed alpha-interferons (patients with resected stage III disease)

Exclusion criteria:

Prior treatment with tyrosinase: 368-376(370D), gp100:209-217(210M), and MART-1:26-35(27L) peptides
Steroid therapy or other immunosuppressive medication requirement
Major systemic infections (e.g., pneumonia or sepsis)
Coagulation or bleeding disorders
Major medical illnesses of the gastrointestinal, cardiovascular, or respiratory systems
Allergic reaction to Montanide ISA 51 (incomplete Freund's adjuvant)
History of uveitis or autoimmune inflammatory eye disease
Other active autoimmune disease
Positive for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody
Pregnant or nursing