Monoclonal Antibody Therapy and Vaccine Therapy in Treating Patients With Resected Stage III or Stage IV Melanoma

Bristol-Myers Squibb (BMS)

Status and phase

Completed

Phase 2

Conditions

Melanoma (Skin)

Intraocular Melanoma

Treatments

Biological: ipilimumab

Biological: Tyrosinase/gp100/MART-1 Peptides

Study type

Interventional

Funder types

Industry

NIH

Identifiers

NCT00084656

CDR0000365467

NCI-6446 (Other Identifier)

MDX010-16 (Other Identifier)

P30CA014089 (U.S. NIH Grant/Contract)

MCC-15241 (Other Identifier)

P30CA076292 (U.S. NIH Grant/Contract)

CA184-016 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Giving monoclonal antibody therapy together with vaccine therapy may be an effective treatment for stage III or stage IV melanoma.

PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with vaccine therapy works in treating patients with resected stage III or stage IV melanoma.

Full description

OBJECTIVES:

Primary

Achieve at least a 40% autoimmune breakthrough event rate, as defined by the induction of grade 1, grade 2, or acceptable grade 3 drug-related autoimmune adverse events, in patients with resected stage III or IV melanoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51.

Secondary

Determine the incidence of drug-related autoimmune adverse events of any grade in patients treated with this regimen.
Determine the time to disease relapse in patients treated with this regimen.
Determine the immunologic response in patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1 of weeks 1, 9, 17, 25, 33, 41, and 53 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51 subcutaneously on day 1 of weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, and 53.

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

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Enrollment

77 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed melanoma
- Stage III (≥ 3 positive lymph nodes) or stage IV disease
- Mucosal or ocular melanoma allowed
Completely resected within the past 6 months
Patients with stage III resected melanoma rendered free of disease may have failed, been ineligible for, or refused prior treatment with interferon alfa
Positive staining of tumor tissue for at least one of the following:
- Antibody HMB-45 for gp100
- Antibody HMB-45 for tyrosinase
- Antibody HMB-45 for MART-1
HLA-A*0201 positive by DNA allele-specific polymerase chain reaction assay

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

At least 6 months

Hematopoietic

WBC ≥ 2,500/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hematocrit ≥ 30%
Hemoglobin ≥ 10 g/dL

Hepatic

AST ≤ 3 times upper limit of normal (ULN)*
Bilirubin ≤ ULN* (< 3.0 mg/dL for patients with Gilbert's syndrome)
No significant hepatic disease that would preclude study participation
Hepatitis B surface antigen negative
Hepatitis C antibody negative NOTE: * Unless attributable to disease

Renal

Creatinine ≤ 2.0 mg/dL
No significant renal disease that would preclude study participation

Cardiovascular

No significant cardiac disease that would preclude study participation

Pulmonary

No significant pulmonary disease that would preclude study participation

Immunologic

No history of any of the following:
- Inflammatory bowel disease or any other autoimmune bowel disease
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Autoimmune ocular disease
No systemic hypersensitivity to Montanide ISA-51 or any vaccine component
No active infection requiring therapy
HIV negative

Other

No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
No significant gastrointestinal disease that would preclude study participation
No significant psychiatric disease that would preclude study participation
No other medical condition that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 4 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)
No prior gp100 antigen, MART-1 antigen, or tyrosinase peptide
At least 4 weeks since prior immunotherapy for melanoma and recovered
No other concurrent immunotherapy

Chemotherapy

At least 4 weeks since prior chemotherapy for melanoma (6 weeks for nitrosoureas) and recovered
No concurrent chemotherapy

Endocrine therapy

At least 4 weeks since prior hormonal therapy for melanoma and recovered
At least 4 weeks since prior systemic, inhaled, or topical corticosteroids
No concurrent systemic, inhaled, or topical corticosteroids

Radiotherapy

At least 4 weeks since prior radiotherapy for melanoma and recovered

Surgery

See Disease Characteristics
At least 4 weeks since prior surgery for melanoma and recovered

Other

No concurrent immunosuppressive agents (e.g., cyclosporine and its analog)
Concurrent analgesic therapy allowed provided the dose is stable for the past 14 days