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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00084656
First received: June 10, 2004
Last updated: April 23, 2010
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Intraocular Melanoma
Melanoma (Skin)
Biological: ipilimumab
Biological: Tyrosinase/gp100/MART-1 Peptides
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: An Extended Dosing, Two-phase Study of MDX-010 as Monotherapy or in Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 VG in the Treatment of Subjects With Resected Stage III or Stage IV Melanoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • First part of study: To achieve at least a 40% immune-related adverse event rate defined by the induction of Grade 1, grade 2, or acceptable grade 3 drug-related immune-related adverse events [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]
  • Second part of study: To determine the time to disease relapse and to determine the rate of acceptable immune-related Grade 1, grade 2, or acceptable grade 3 drug-related immune-related adverse events [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine incidence of drug-related irAEs (1st & 2nd part) through clinical and laboratory assessment of immune-related adverse events [ Time Frame: 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]
  • Determine time to disease relapse (1st part) through diagnostic imaging assessments, including brain MRI [ Time Frame: Approximately every 3 months] ] [ Designated as safety issue: No ]
  • Determine immunologic response (1st & 2nd part) through assay of peripheral blood samples [ Time Frame: Weeks 1, 9, 11, 17, 21, 25, 33, 41, and 53 ] [ Designated as safety issue: Yes ]
  • Evaluate toxicity profile (1st & 2nd part) through clinical and laboratory assessment of adverse events [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]

Enrollment: 75
Study Start Date: May 2004
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Biological: 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)
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.)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084656

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00084656     History of Changes
Other Study ID Numbers: CDR0000365467, P30CA076292, P30CA014089, MCC-15241, MDX010-16, NCI-6446, CA184-016
Study First Received: June 10, 2004
Last Updated: April 23, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
stage III melanoma
stage IV melanoma
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
iris melanoma
recurrent melanoma
recurrent intraocular melanoma
metastatic intraocular melanoma

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases

ClinicalTrials.gov processed this record on September 18, 2014