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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00084656
Recruitment Status : Completed
First Posted : June 11, 2004
Last Update Posted : April 26, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE June 10, 2004
First Posted Date  ICMJE June 11, 2004
Last Update Posted Date April 26, 2010
Study Start Date  ICMJE May 2004
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2010)
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00084656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2010)
  • 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 ]
  • Determine time to disease relapse (1st part) through diagnostic imaging assessments, including brain MRI [ Time Frame: Approximately every 3 months] ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Monoclonal Antibody Therapy and Vaccine Therapy in Treating Patients With Resected Stage III or Stage IV Melanoma
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Intraocular Melanoma
  • Melanoma (Skin)
Intervention  ICMJE
  • 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.)
Study Arms Experimental: Arm 1
Interventions:
  • Biological: ipilimumab
  • Biological: Tyrosinase/gp100/MART-1 Peptides
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2010)
75
Original Enrollment  ICMJE Not Provided
Study Completion Date Not Provided
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00084656
Other Study ID Numbers  ICMJE CDR0000365467
P30CA076292 ( U.S. NIH Grant/Contract )
P30CA014089 ( U.S. NIH Grant/Contract )
MCC-15241 ( Other Identifier: Moffitt Cancer Center )
MDX010-16 ( Other Identifier: Medarex )
NCI-6446 ( Other Identifier: National Cancer Institute )
CA184-016 ( Other Identifier: BMS )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Study Director, Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP