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

NCT ID: NCT00084656

Last Updated: 2022-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2009-10-31

Brief Summary

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.

Detailed 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.

Conditions

Intraocular Melanoma; Melanoma (Skin)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

ipilimumab

Intervention Type: BIOLOGICAL

IV over 90 mins on day 1, wks 1,9,17,25,33,41,53 Dose: 3 mg/kg (Part I), 10 mg/kg (Part II)

Tyrosinase/gp100/MART-1 Peptides

Intervention Type: BIOLOGICAL

(All subjects in Part I and HLA-A\*0201 positive subjects only in Part II): SC, day 1 of wks 1,3,5,7,9,11,17, 21,25,33,41,53 Dose: 1 mg peptide emulsified in 1 mL Montanide ISA 51 VG.)

Interventions

ipilimumab

IV over 90 mins on day 1, wks 1,9,17,25,33,41,53 Dose: 3 mg/kg (Part I), 10 mg/kg (Part II)

Intervention Type: BIOLOGICAL

Tyrosinase/gp100/MART-1 Peptides

(All subjects in Part I and HLA-A\*0201 positive subjects only in Part II): SC, day 1 of wks 1,3,5,7,9,11,17, 21,25,33,41,53 Dose: 1 mg peptide emulsified in 1 mL Montanide ISA 51 VG.)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Countries

United States

References

Garg SK, Ott MJ, Mostofa AGM, Chen Z, Chen YA, Kroeger J, Cao B, Mailloux AW, Agrawal A, Schaible BJ, Sarnaik A, Weber JS, Berglund AE, Mule JJ, Markowitz J. Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy. Front Immunol. 2020 Feb 25;11:164. doi: 10.3389/fimmu.2020.00164. eCollection 2020.

Reference Type: DERIVED

PMID: 32161584 (View on PubMed)

Sarnaik AA, Yu B, Yu D, Morelli D, Hall M, Bogle D, Yan L, Targan S, Solomon J, Nichol G, Yellin M, Weber JS. Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma. Clin Cancer Res. 2011 Feb 15;17(4):896-906. doi: 10.1158/1078-0432.CCR-10-2463. Epub 2010 Nov 24.

Reference Type: DERIVED

PMID: 21106722 (View on PubMed)

Other Identifiers

P30CA076292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014089

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MCC-15241

Identifier Type: OTHER

Identifier Source: secondary_id

MDX010-16

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-6446

Identifier Type: OTHER

Identifier Source: secondary_id

CA184-016

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000365467

Identifier Type: -

Identifier Source: org_study_id