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MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00094653
Collaborator
(none)
1,783
Enrollment
209
Locations
3
Arms
61
Duration (Months)
8.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response [PR/CR]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.

Condition or Disease Intervention/Treatment Phase
  • Drug: MDX-010 (anti-CTLA4) monoclonal antibody
  • Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine
 Phase 3

Detailed Description

Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.

Study Design

Study Type:
Interventional
Actual Enrollment :
1783 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Multicenter Study Comparing MDX-010 Monotherapy, MDX-010 in Combination With a Melanoma Peptide Vaccine, and Melanoma Vaccine Monotherapy in HLA-A2*0201-Positive Patients With Previously Treated Unresectable Stage III or IV Melanoma
Study Start Date :
Sep 1, 2004
Actual Primary Completion Date :
Aug 1, 2009
Actual Study Completion Date :
Oct 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 1

Melanoma Peptide Vaccine (MDX-1379) (gp100) + Placebo

Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine
2mL (2 subcutaneous injections of 2 mL each, 1 to each thigh), every 3 weeks for 4 doses.
Other Names:
  • melanoma peptide vaccine

    		•
    Experimental: 2

    MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine)

    Drug: MDX-010 (anti-CTLA4) monoclonal antibody
    3mg/kg (intravenous [iv] infusion over 90 minutes), every 3 weeks for 4 doses
    Other Names:
  • ipilimumab

    • Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine
    2mL (2 subcutaneous injections of 2 mL each, 1 to each thigh), every 3 weeks for 4 doses.
    Other Names:
  • melanoma peptide vaccine

    		•
    Active Comparator: 3

    MDX-010 (ipilimumab) + Placebo

    Drug: MDX-010 (anti-CTLA4) monoclonal antibody
    3mg/kg (intravenous [iv] infusion over 90 minutes), every 3 weeks for 4 doses
    Other Names:
  • ipilimumab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone [From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)]

      OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    Secondary Outcome Measures

    1. Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy [From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)]

      OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    2. 12-, 18-, and 24-Month Survival Rates [Month 12, Month 18, Month 24]

      The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.

    3. Progression Free Survival (PFS) [From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)]

      PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    4. Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24 [Week 12, Week 24]

      PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.

    5. Time to Progression (TTP) [from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks])]

      TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.

    6. Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD) [BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.]

      Investigator's assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations >=4 weeks apart, no evidence of PD. PR: >=50% ↓ in sum of products of longest diameter & greatest perpendicular diameter of all target lesions compared to baseline by 2 observations >=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ >=25% in sum of products of longest diameter & greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of >= 1 new lesion.

    7. Determination of Best Overall Response Rate (BORR) [Up to week 24]

      Response was based on the investigators' assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.

    8. Time to Response [From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)]

      Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.

    9. Duration of Response [from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])]

      Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).

    10. Disease Control Rate (DCR) [Up to week 24]

      Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.

    11. Delayed Response (Response Beyond Week 24) [from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])]

      Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.

    12. Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12 [Baseline (Day 1, Cycle1), Week 12]

      The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).

    13. Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death [On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).]

      An AE was defined as any undesirable sign, symptom, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be treatment-related. Adverse events are graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. If CTCAE grading does not exist for an adverse event, the intensity of mild (1), moderate (2), severe (3), and life-threatening (4) were used.

    14. Percentage of Participants With Immune-Related Adverse Events (irAEs) [On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).]

      An immune related adverse event (irAE) was defined as an adverse event of unknown etiology, associated with study drug exposure and consistent with an immune phenomenon. The irAEs were programmatically determined from a predefined list of MedDRA version 12.0 high-level group terms, high-level terms and preferred terms of all ipilimumab related adverse event. The category of "Other irAEs" includes blood, eye, immune, infections, renal, and respiratory systems.

    15. Percentage of Participants With Worst On-Study Hematological Abnormalities [On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).]

      ANC=Absolute Neutrophil Count. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

    16. Percentage of Participants With Worst On-Study Liver Abnormalities [On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).]

      ALT=alanine aminotransferase; AST=aspartate aminotransferase. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

    17. Percentage of Participants With Worst On-Study Renal Abnormalities [On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).]

      CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.

    18. Clinically Meaningful Changes in Vital Signs and Physical Examinations [vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter]

      Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosed with malignant melanoma

    • Measurable unresectable Stage III or IV melanoma

    • HLA-A*0201 positive

    • Previous treatment with & failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide

    • At least 4 weeks since prior treatment

    • Negative pregnancy

    • Life expectancy greater than 4 months

    • Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1

    • Required lab values

    • Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative

    Exclusion Criteria:

    • Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer

    • Ocular melanoma

    • Active, untreated central nervous system (CNS) metastasis

    • Prior treatment with MDX-010 (anti-CTLA4) antibody

    • Prior treatment with any cancer therapeutic vaccine

    • Active autoimmune disease or history of autoimmune disease

    • Pregnancy or nursing

    • Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)

    • Underlying medical conditions deemed hazardous if treated with study drug

    • Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids

    • Unable to provide informed consent

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Cancer Center Tucson Arizona United States 85724
    2 University Medical Center Tucson Arizona United States 85724
    3 City of Hope National Medical Center Duarte California United States 91010
    4 San Diego Cancer Center Encinitas California United States 92024
    5 La Jolla Hematology and Oncology Medical Group La Jolla California United States 92037
    6 Scripps Cancer Center La Jolla California United States 92037
    7 Moores UCSD Cancer Center La Jolla California United States 92093
    8 Pacific Shores Medical Group Long Beach California United States 90813
    9 Cancer Institute Medical Group, Inc Los Angeles California United States 90025
    10 The Angeles Clinic and Research Institute Los Angeles California United States 90025
    11 USC/Norris Comprehensive Cancer Center Los Angeles California United States 90033
    12 North County Oncology Medical Clinical, Inc. Oceanside California United States 92056
    13 City of Hope Medical Group Pasadena California United States 91105
    14 University of California, San Diego San Diego California United States 92103
    15 St. Mary's Medical Center - Northern California Melanoma Center San Francisco California United States 94109
    16 Cancer Institute Medical Group, Inc Santa Monica California United States 90404
    17 San Diego Cancer Center Vista California United States 92081
    18 Anschutz Cancer Pavilion Aurora Colorado United States 80010
    19 Rocky Mountain Cancer Centers Aurora Colorado United States 80012
    20 University of Colorado Health Sciences Center Aurora Colorado United States 80045
    21 Rocky Mountain Cancer Centers Boulder Colorado United States 80304
    22 Rocky Mountain Cancer Centers Colorado Springs Colorado United States 80909
    23 Rocky Mountain Cancer Centers Denver Colorado United States 80218
    24 University of Colorado Hospital Denver Colorado United States 80262
    25 Rocky Mountain Cancer Centers Lakewood Colorado United States 80228
    26 Rocky Mountain Cancer Centers Littleton Colorado United States 80120
    27 Rocky Mountain Cancer Centers Lone Tree Colorado United States 80124
    28 Rocky Mountain Cancer Centers Longmont Colorado United States 80501
    29 Yale University School of Medicine - Oncology Outpatient Clinic New Haven Connecticut United States 06520
    30 Mount Sinai Comprehensive Cancer Center at Aventura Aventura Florida United States 33180
    31 Memorial Regional Cancer Center Hollywood Florida United States 33021
    32 Shands Jacksonville Jacksonville Florida United States 32209
    33 University of Florida/Jacksonville Faculty Clinic Jacksonville Florida United States 32209
    34 Mount Sinai Comprehensive Cancer Center Miami Beach Florida United States 33140
    35 Mount Sinai Medical Center Miami Beach Florida United States 33140
    36 Jackson Memorial Hospital & Clinics Miami Florida United States 33136
    37 University of Miami Hospital & Clinics Miami Florida United States 33136
    38 M.D. Anderson Cancer Center Orlando Orlando Florida United States 32806
    39 Palm Beach Cancer Institute Palm Beach Gardens Florida United States 33410
    40 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612
    41 Palm Beach Cancer Institute Wellington Florida United States 33414
    42 Palm Beach Cancer Institute West Palm Beach Florida United States 33401
    43 Emory University Hospital-Winship Cancer Institute Atlanta Georgia United States 30322
    44 Cancer Care Specialists of Central IL Decatur Illinois United States 62526
    45 Decatur Memorial Hospital Decatur Illinois United States 62526
    46 Cancer Care Specialists of Central IL Effingham Illinois United States 62401
    47 Cardinal Bernardin Cancer Center, Loyola Unv. Med. Ctr. Maywood Illinois United States 60153
    48 Center for Cancer Care at Goshen Health System Goshen Indiana United States 46526
    49 Indiana Oncology Hematology Consultants North Indianapolis Indiana United States 46202
    50 American Health Network of IN, LLC Indianapolis Indiana United States 46237
    51 Indiana Oncology Hematology South Indianapolis Indiana United States 46237
    52 Indiana Oncology Hematology Consutants of Noblesville Noblesville Indiana United States 46060
    53 Central Baptist Hospital Lexington Kentucky United States 40503
    54 James Graham Brown Cancer Center Louisville Kentucky United States 40202
    55 Norton Hospital Louisville Kentucky United States 40202
    56 University of Louisville Hospital Louisville Kentucky United States 40202
    57 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231
    58 Franklin Square Hospital Center Baltimore Maryland United States 21237
    59 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Lutherville Maryland United States 21093
    60 Beth Isreal Dec Medical Center Boston Massachusetts United States 02115
    61 Brigham and Womens Hospital Boston Massachusetts United States 02115
    62 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    63 Henry Ford Medical Center Dearborn Michigan United States 48126
    64 Henry Ford Hospital Detroit Michigan United States 48202
    65 Henry Ford Medical Center- West Bloomfield West Bloomfield Michigan United States 48322
    66 Humphrey Cancer Center Coon Rapids Minnesota United States 55433
    67 Humphrey Cancer Center Fridley Minnesota United States 55432
    68 Hubert H Humphrey Cancer Center Robbinsdale Minnesota United States 55422
    69 Family Cancer Center Olive Branch Mississippi United States 38654
    70 Ellis Fischel Cancer Center Columbia Missouri United States 65203
    71 St. Joseph Oncology, Inc St. Joseph Missouri United States 64507
    72 Barnes Jewish Hospital St. Louis Missouri United States 63110
    73 Washington Unv. School of Med./ Siteman Cancer Center St. Louis Missouri United States 63110
    74 Hackensack University Medical Center Hackensack New Jersey United States 07601
    75 The Cancer Center at Hackensack University Medical Center Hackensack New Jersey United States 07601
    76 Hematology-Oncology Associates of Northern NJ, PA Morristown New Jersey United States 07962
    77 Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08901
    78 The Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
    79 Overlook Oncology Center Summit New Jersey United States 07901
    80 New Mexico Oncology Hematology Consultants, Ltd. Albuquerque New Mexico United States 87109
    81 Hematology-Oncology Associates of CNY East Syracuse New York United States 13057
    82 Memorial Sloan Kettering Cancer Center New York New York United States 10021
    83 Columbia University Medical Center, Irving Center for Clinical Research New York New York United States 10032
    84 University of North Carolina at Chapel Hill Chapel Hill North Carolina United States 27599-7050
    85 The Christ Hospital Cancer Center Cincinnati Ohio United States 45219
    86 The Cleveland Clinic Foundation Cleveland Ohio United States 44195
    87 Providence Portland Medical Center Portland Oregon United States 97213
    88 The Oregon Clinical Portland Oregon United States 97213
    89 Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
    90 Thomas Jefferson University Hosptital Philadelphia Pennsylvania United States 19107
    91 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    92 Hillman Cancer Research Pavilion Pittsburgh Pennsylvania United States 15213
    93 Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    94 University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania United States 15232
    95 Cancer Centers of the Carolinas Easley South Carolina United States 29640
    96 Cancer Centers of the Carolinas Greenville South Carolina United States 29615
    97 Cancer Centers of the Carolinas Seneca South Carolina United States 29672
    98 Cancer Centers of the Carolinas Spartanburg South Carolina United States 29307
    99 Family Cancer Center Bartlett Tennessee United States 38133
    100 Family Cancer Center Collierville Tennessee United States 38017
    101 Family Cancer Center Memphis Tennessee United States 38119
    102 The West Clinic Memphis Tennessee United States 38120
    103 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    104 Arlington Cancer Center Arlington Texas United States 76012
    105 Center for Oncology Research and Treatment Dallas Texas United States 75230
    106 Joe Arrington Cancer Research and Treatment Center Lubbock Texas United States 79410
    107 Center for Oncology Research and Treatment Richardson Texas United States 75080
    108 Huntsman Cancer Institute Salt Lake City Utah United States 84112-5550
    109 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    110 Fletcher Allen Health Care Burlington Vermont United States 05405
    111 Hospital Municipal de Oncoligia Maria Curie Ciudad de Buenos Aires Buenos Aires Argentina
    112 Instituto Medico Platense La Plata Provincia de Buenos Aires Argentina 1900
    113 Hospital Militar Central Buenos Aires Argentina
    114 Instituto Medico Especializado Alexander Fleming Buenos Aires Argentina
    115 Hospital Britanico de Buenos Aires Ciudad de Buenos Aires Argentina C1280AEB
    116 Hospital Municipal de Oncologia Maria Curie Ciudad de Buenos Aires Argentina C1405BWU
    117 Hospital General de Agudos Carlos G. Durand Ciudad de Buenos Aires Argentina C1405DCS
    118 Instituto de Oncologia Angel H. Roffo Ciudad de Buenos Aires Argentina C1417DTB
    119 Hospital Militar Central Ciudad de Buenos Aires Argentina C1426BOS
    120 Instituto Alexander Fleming Ciudad de Buenos Aires Argentina C1426DRB
    121 Hospital Privado de Cordoba S.A. Cordoba Argentina X5016KEH
    122 Hospital Privado Centro Medico de Cordoba S.A. Cordoba Argentina
    123 ISIS Clinica Especializada Santa Fe Argentina S3000FFU
    124 ISIS Clinica Especializada Santa Fe Argentina
    125 Institut Jules Bordet Brussels Belgium 1000
    126 Erasme Hospital, Free Universtiy of Brussels Brussels Belgium 1070
    127 Erasme Hospital Brussels Belgium 1070
    128 U.Z. Gent Gent Belgium 9000
    129 Universitair Ziekenhuis Gasthuisberg Leuven Belgium 3000
    130 Cliniques Universitaires UCL de Mont-Godinne Yvoir Belgium 5530
    131 Hospital Araujo Jorge da Associacoa de Combate ao Cancer em Goias Goiania GO Brazil
    132 Pro Onco Centro Tratamento Oncologico Londrina PR Brazil
    133 Hospital Sao Lucas da PUCRS Porto Alegre RS Brazil
    134 Fundacao Pio XII - Hospital de Cancer de Barretos Barretos SP Brazil
    135 Fundacoa Hospital Amaral Carvalho Jau SP Brazil
    136 Santo Andre Diagnosticos aTratamentos Santo Andre SP Brazil
    137 Sociedade Beneficante de Sennores - Hospital Sino Libante Sao Paulo SP Brazil
    138 Hospital de Cancer de Barretos - Fundacao Pio XII Barretos - SP Brazil 14784-400
    139 Biocor - Hosp. de Doencas Cardiovasculares Ltda. Belo Horizonte - MG Brazil 34000-000
    140 Hospital Araujo Jorge Goiania - GO Brazil 74605-070
    141 Pro Onco Centro Tratemento Oncologico Londrina - PR Brazil 86050-190
    142 Fund. SOAD / HC de Porto Alegre Porto Alegre - RS Brazil 90035-003
    143 Hospital Sao Lucas - PUCRS Porto Alegre - RS Brazil 90610-000
    144 Fundacao Central Sul-Americana para o Desenvolvimento de Drogas Anticancer-SOAD Porto Alegre Brazil 90035-003
    145 Santo Andre Diagnosticos e Tratamentos Ltda. Santo Andre-SP Brazil 09090-780
    146 HC-FMUSP Sao Paulo - SP Brazil 05403-000
    147 Hospital Sirio Labanes Sao Paulo-SP Brazil 01308-050
    148 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    149 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    150 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
    151 Dr. H. Bliss Murphy Cancer Centre St. John's Newfoundland and Labrador Canada A1B 3V6
    152 Cancer Centre of Southeastern Ontario at KGH Kingston Ontario Canada K7L 5P9
    153 London Regional Cancer Program London Ontario Canada N6A 4L6
    154 The Ottawa Hospital Regional Cancer Centre Ottawa Ontario Canada K1H 8L6
    155 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
    156 Sir Mortimer B. Davis - Jewish General Hospital Montreal Quebec Canada H3T 1E2
    157 Instituto Nacional del Cancer Independencia Santiago Chile
    158 Clinica Davila Recoleta Santiago Chile
    159 Clinica Renaca Renaca Vina Del Mar Chile
    160 Fundacion Arturo Lopez Perez Santiago Chile
    161 Hospital Barros Luco Santiago Chile
    162 Centre Oscar Lambret Lille France 59020 Cedex
    163 Centre Leon Berard Lyon France 69373 Cedex 08
    164 Hopital Sainte-Marguerite Marseille France 13009
    165 Hopital Saint-Eloi Montpellier France 34295 Cedex 5
    166 Hotel Dieu Nantes France 44093 Cedex 1
    167 Centre Antoine Lacassagne Nice cedex 2 France 06189
    168 Hopital Saint-Louis Paris France 75010 10
    169 Centre Eugene Marquis Rennes France 35042 Cedex
    170 Centre-Hospitalier Universitaire de Saint-Etienne Saint-Etienne France 42055 Cedex 2
    171 Centre Alexis Vautrin Vandoeuvre les Nancy France 54511 Cedex
    172 Institut Gustave Roussy (IGR) Villejuif France 94805 Cedex
    173 Klinik fur und Poliklinik fur Dermatologie, Venerologie und Allergologie Hufelandstr. 55 Essen Germany 45122
    174 Klinikum Augsburg Augsburg Germany 86156
    175 Charite Universitaets medizin Berlin Berlin Germany 10117
    176 Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin Berlin Germany 12200
    177 Universitaetsklinikum Dusseldorf Duesseldorf Germany 40225
    178 Universitaetsklinikum Erlangen Erlangen Germany 91052
    179 Universitaetsklinikum Essen Essen Germany 45122
    180 Universitaetsklinikum Heidelberg Heidelburg Germany 69115
    181 Klinikum der Friedrich-Schiller-Universitaet Jena Jena Germany 07740
    182 Klinikum Mannheim gGmbH Mannheim Germany 68167
    183 University of Mannheim Mannheim Germany
    184 Klinikum Rechts der Isar / TU Muenchen Muenchen Germany 81675
    185 Universitaetsklinikum Tuebingen Tuebingen Germany 72076
    186 Universitaetsklinikum Wuerzburg Wuerzburg Germany 97080
    187 National Institute of Oncology Budapest Hungary H-1122
    188 University of Debrecen, Medical and Health Sciences Center Debrecen Hungary H-4012
    189 Semmelweis Hospital Miskolc Hungary H-3529
    190 University of Szeged, Albert Szent-Gyorgyi Medical and Pharmaceutical Center Szeged Hungary H-6720
    191 Antoni Van Leeuwenhoek Ziekenhuis Amsterdam Netherlands 1066 CX
    192 Vrije Universiteit Medisch Centrum (VUMC) Amsterdam Netherlands 1081 HV
    193 Academisch Ziekenhuis Maastricht Maastricht Netherlands 6229 HX
    194 Mary Potter Oncology Centre Groenkloof South Africa 0181
    195 GVI Oncology Panorama South Africa 7500
    196 Mary Potter Oncology Centre Pretoria South Africa 0181
    197 Sandton Onocology Medical Research Sandton South Africa 2199
    198 Centre Hospitalier Universitaire Vaudois - CHUV Lausanne Rue du Bugnon 46 Switzerland CH-1011
    199 Centre Hospitalier Universitaire Vaudois - CHUV Lausanne Switzerland CH-1011
    200 Dermatologische Klinik Universitatsspital Zurich Zurich Switzerland 8091
    201 St. Luke's Cancer Center, The Royal Surrey County Hospital Guildford Surry United Kingdom GU2 7XX
    202 Velindre Hospital Cardiff United Kingdom CF14 2TL
    203 Ninewells Hospital Dundee United Kingdom DD1 9SY
    204 Christie Hospital Manchester United Kingdom M20 4BX
    205 Nottingham City Hospital Nottingham United Kingdom NG5 1PB
    206 Churchill Hospital Oxford United Kingdom OX3 7LJ
    207 Poole Hospital Poole United Kingdom BH15 2JB
    208 Weston Park Hospital Sheffield United Kingdom S10 2SJ
    209 Southampton General Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00094653
    Other Study ID Numbers:
    • MDX010-20
    • CA184-002
    First Posted:
    Oct 22, 2004
    Last Update Posted:
    Jul 11, 2011
    Last Verified:
    Jun 1, 2011
    Keywords provided by , ,
    melanoma
    metastatic melanoma
    skin cancer
    Additional relevant MeSH terms:
    Melanoma
    Ipilimumab
    Vaccines
    Antibodies
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Of the 1783 participants who enrolled and were screened for study participation, a total of 676 subjects were randomized.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Period Title: Overall Study
    STARTED 403 137 136
    Treated 381 131 131
    COMPLETED 82 31 10
    NOT COMPLETED 321 106 126

    Baseline Characteristics

    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100 Total
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Total of all reporting groups
    Overall Participants 403 137 136 676
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    55.6
    56.8
    57.4
    56.2
    Age, Customized (participants) [Number]
    < 65 years
    291
    72.2%
    95
    69.3%
    94
    69.1%
    480
    71%
    >=65 years
    112
    27.8%
    42
    30.7%
    42
    30.9%
    196
    29%
    Sex: Female, Male (Count of Participants)
    Female
    156
    38.7%
    56
    40.9%
    63
    46.3%
    275
    40.7%
    Male
    247
    61.3%
    81
    59.1%
    73
    53.7%
    401
    59.3%
    Race/Ethnicity, Customized (Number) [Number]
    White
    380
    94.3%
    129
    94.2%
    129
    94.9%
    638
    94.4%
    Black
    3
    0.7%
    1
    0.7%
    1
    0.7%
    5
    0.7%
    Hispanic
    18
    4.5%
    7
    5.1%
    5
    3.7%
    30
    4.4%
    Other
    2
    0.5%
    0
    0%
    1
    0.7%
    3
    0.4%
    Duration of Melanoma (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    5.09
    4.34
    5.65
    5.05
    Melanoma Stage (Number) [Number]
    M0
    5
    1.2%
    1
    0.7%
    4
    2.9%
    10
    1.5%
    M1a
    37
    9.2%
    14
    10.2%
    11
    8.1%
    62
    9.2%
    M1b
    76
    18.9%
    22
    16.1%
    23
    16.9%
    121
    17.9%
    M1c
    285
    70.7%
    100
    73%
    98
    72.1%
    483
    71.4%
    Prior Interleukin-2 Therapy (Number) [Number]
    No
    314
    77.9%
    105
    76.6%
    103
    75.7%
    522
    77.2%
    Yes
    89
    22.1%
    32
    23.4%
    33
    24.3%
    154
    22.8%
    Lactate Dehydrogenase (Number) [Number]
    >upper limit of normal (ULN)
    149
    37%
    53
    38.7%
    52
    38.2%
    254
    37.6%
    <=ULN
    252
    62.5%
    84
    61.3%
    81
    59.6%
    417
    61.7%
    unknown
    2
    0.5%
    0
    0%
    3
    2.2%
    5
    0.7%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone
    Description OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
    Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 136
    Median (95% Confidence Interval) [months]
    9.95
    6.44
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method Stratified Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.55 to 0.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    2. Secondary Outcome
    Title Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy
    Description OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
    Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Median (95% Confidence Interval) [months]
    9.95
    10.12
    6.44
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0026
    Comments
    Method Stratified Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.66
    Confidence Interval (2-Sided) 95%
    0.51 to 0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7575
    Comments
    Method Stratified Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.83 to 1.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) and log-rank test p-values were stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    3. Secondary Outcome
    Title 12-, 18-, and 24-Month Survival Rates
    Description The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.
    Time Frame Month 12, Month 18, Month 24

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    12-Month Survival Rate
    0.436
    0.456
    0.253
    18-Month Survival Rate
    0.300
    0.332
    0.163
    24-Month Survival Rate
    0.216
    0.235
    0.137
    4. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
    Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study. Subjects who neither progressed nor died were censored at the date of the last tumor assessment.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Median (95% Confidence Interval) [months]
    2.76
    2.86
    2.76
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.66 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.64
    Confidence Interval (2-Sided) 95%
    0.50 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    1.01 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    5. Secondary Outcome
    Title Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
    Description PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
    Time Frame Week 12, Week 24

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Week 12
    0.491
    0.1%
    0.577
    0.4%
    0.485
    0.4%
    Week 24
    0.164
    0%
    0.240
    0.2%
    0.100
    0.1%
    6. Secondary Outcome
    Title Time to Progression (TTP)
    Description TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.
    Time Frame from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks])

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Median (95% Confidence Interval) [months]
    2.76
    2.86
    2.76
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.66 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.64
    Confidence Interval (2-Sided) 95%
    0.50 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    1.01 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox model for Hazard ratios (HR) were stratified by M-stage at randomization (M0, M1a, M1b vs. M1c) and prior treatment with IL-2 (Yes vs. No).
    7. Secondary Outcome
    Title Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
    Description Investigator's assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations >=4 weeks apart, no evidence of PD. PR: >=50% ↓ in sum of products of longest diameter & greatest perpendicular diameter of all target lesions compared to baseline by 2 observations >=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ >=25% in sum of products of longest diameter & greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of >= 1 new lesion.
    Time Frame BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Complete Response
    1
    0.2%
    2
    1.5%
    0
    0%
    Partial Response
    22
    5.5%
    13
    9.5%
    2
    1.5%
    Stable Disease
    58
    14.4%
    24
    17.5%
    13
    9.6%
    Progressed Disease
    239
    59.3%
    70
    51.1%
    89
    65.4%
    Not Evaluated, Missing, or Unknown
    83
    20.6%
    28
    20.4%
    32
    23.5%
    8. Secondary Outcome
    Title Determination of Best Overall Response Rate (BORR)
    Description Response was based on the investigators' assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.
    Time Frame Up to week 24

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Number (95% Confidence Interval) [percentage of participants]
    5.7
    1.4%
    10.9
    8%
    1.5
    1.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0433
    Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0012
    Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0402
    Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
    Method Cochran-Mantel-Haenszel
    Comments
    9. Secondary Outcome
    Title Time to Response
    Description Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.
    Time Frame From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)

    Outcome Measure Data

    Analysis Population Description
    Responder subjects in intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 23 15 2
    Mean (Full Range) [months]
    3.324
    (0.9561)
    3.176
    (0.7629)
    2.743
    (0.0697)
    10. Secondary Outcome
    Title Duration of Response
    Description Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).
    Time Frame from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])

    Outcome Measure Data

    Analysis Population Description
    Responders only in intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study. Patients who did not progress or died were censored at the date of their last tumor assessment.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 23 15 2
    Median (95% Confidence Interval) [months]
    11.47
    NA
    NA
    11. Secondary Outcome
    Title Disease Control Rate (DCR)
    Description Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.
    Time Frame Up to week 24

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat population, as randomized. All subjects who were randomized to any treatment group in the study.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 403 137 136
    Number (95% Confidence Interval) [percentage of participants]
    20.1
    5%
    28.5
    20.8%
    11.0
    8.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0179
    Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0429
    Comments P-values were computed using CMH test stratified by baseline M-stage at randomization (M0, M1a, M1b vs. M1c) and prior IL-2 treatment (Yes vs. No).
    Method Cochran-Mantel-Haenszel
    Comments
    12. Secondary Outcome
    Title Delayed Response (Response Beyond Week 24)
    Description Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.
    Time Frame from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])

    Outcome Measure Data

    Analysis Population Description
    Number of subjects with BOR of PR/SD (80 subjects ipi + gp100 , 37 ipi , 15 gp100) plus number of subjects with BOR of PD that had subsequent evaluation (8 ipi + gp100, 3 ipi, 3 gp100).
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 88 40 18
    Complete Response Beyond Week 24
    1
    0.2%
    3
    2.2%
    0
    0%
    Partial Response Beyond Week 24
    3
    0.7%
    2
    1.5%
    0
    0%
    Stable Disease Beyond Week 24
    3
    0.7%
    0
    0%
    0
    0%
    13. Secondary Outcome
    Title Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12
    Description The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).
    Time Frame Baseline (Day 1, Cycle1), Week 12

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication. N=number of participants analyzed, n=number of participants with measure at given time points.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 381 131 131
    Global QOL (n=226, 83, 77)
    -7.4
    -8.8
    -10.4
    Physical (n=226 83, 78)
    -6.2
    -5.1
    -10.1
    Role Change (n=226, 83, 78)
    -9.3
    -10.5
    -13.7
    Cognitive (n=226, 83, 78)
    -3.1
    -4.3
    -3.4
    Emotional (n=227, 83, 78)
    -1.5
    -3.6
    -1.5
    Social (n=227, 83, 76)
    -5.6
    -7.5
    -4.2
    Fatigue (n=226, 82, 78)
    10.6
    12.5
    14.5
    Nausea and Vomiting (n=226, 83, 78)
    4.6
    3.1
    4.4
    Pain (n=227, 83, 78)
    5.6
    7.9
    11.9
    Dyspnea (n=222, 81, 77)
    3.5
    5.3
    9.1
    Sleep Disturbance (n=225, 83, 76)
    6.5
    10.1
    11.0
    Appetite Loss (n=225, 83, 78)
    8.5
    11.6
    10.3
    Constipation (n=225, 83, 77)
    5.2
    1.9
    11.8
    Diarrhea (n=223, 82, 78)
    6.4
    9.1
    2.1
    Financial Impact (n=226, 83, 76)
    0.0
    3.1
    1.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Global quality of life change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2805
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.0
    Confidence Interval (2-Sided) 95%
    -2.5 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Global quality of life change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6300
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.6
    Confidence Interval (2-Sided) 95%
    -5.0 to 8.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Global quality of life change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6026
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -3.9 to 6.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Physical change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1219
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.9
    Confidence Interval (2-Sided) 95%
    -1.1 to 8.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Physical change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0978
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.0
    Confidence Interval (2-Sided) 95%
    -0.9 to 11.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Physical change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6590
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -6.0 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Role change, change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2480
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.3
    Confidence Interval (2-Sided) 95%
    -3.0 to 11.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Role change, change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4742
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.2
    Confidence Interval (2-Sided) 95%
    -5.6 to 12.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Role change, change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7597
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    -6.1 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Cognitive change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9119
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -4.7 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Cognitive change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7616
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -6.9 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Cognitive change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6266
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    -3.6 to 6.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Emotional change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9984
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -4.8 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Emotional change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4873
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -7.8 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Emotional change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3938
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.0
    Confidence Interval (2-Sided) 95%
    -2.7 to 6.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Social change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6695
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -8.1 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Social change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4041
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.4
    Confidence Interval (2-Sided) 95%
    -11.3 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Social change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5538
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.9
    Confidence Interval (2-Sided) 95%
    -4.5 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Fatigue change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2259
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.9
    Confidence Interval (2-Sided) 95%
    -10.3 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Fatigue change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6168
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -9.6 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Fatigue change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5329
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -8.2 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Nausea and Vomiting change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9397
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -4.7 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Nausea and Vomiting change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6716
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -7.1 to 4.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Nausea and Vomiting change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5497
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -3.3 to 6.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Pain change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0625
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.3
    Confidence Interval (2-Sided) 95%
    -12.8 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Pain change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3214
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.0
    Confidence Interval (2-Sided) 95%
    -11.9 to 3.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Pain change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4898
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -8.7 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Dyspnea change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0761
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.6
    Confidence Interval (2-Sided) 95%
    -11.8 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Dyspnea change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3187
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -11.2 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Dyspnea change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5548
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -7.9 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 31
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Sleep disturbance change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2450
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.5
    Confidence Interval (2-Sided) 95%
    -12.1 to 3.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 32
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Sleep disturbance change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8464
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -10.0 to 8.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 33
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Sleep Disturbance change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3351
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.6
    Confidence Interval (2-Sided) 95%
    -10.9 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 34
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Appetite loss change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6291
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -9.1 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 35
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Appetite Loss change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7675
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    -7.4 to 10.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 36
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Appetite Loss change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3911
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -10.2 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 37
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Constipation change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0431
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.5
    Confidence Interval (2-Sided) 95%
    -12.9 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 38
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Constipation change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0101
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -9.9
    Confidence Interval (2-Sided) 95%
    -17.4 to -2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 39
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Constipation change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2796
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.4
    Confidence Interval (2-Sided) 95%
    -2.8 to 9.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 40
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Diarrhea change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1940
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.3
    Confidence Interval (2-Sided) 95%
    -2.2 to 10.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 41
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Diarrhea change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0821
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.9
    Confidence Interval (2-Sided) 95%
    -0.9 to 14.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 42
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Diarrhea change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4169
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -9.0 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 43
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Financial Impact change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5717
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -7.5 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 44
    Statistical Analysis Overview Comparison Group Selection gp100, gp100
    Comments Financial Impact change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -5.6 to 8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    Statistical Analysis 45
    Statistical Analysis Overview Comparison Group Selection Ipilimumab Plus gp100, gp100
    Comments Financial Impact change from baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2849
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -8.8 to 2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Least square mean can be defined as a linear combination of estimated effects, from a linear model. These means are based on ANCOVA model with covariate variables as baseline score, M-stage and prior-IL2 treatment at randomization, and treatment.
    14. Secondary Outcome
    Title Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
    Description An AE was defined as any undesirable sign, symptom, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be treatment-related. Adverse events are graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. If CTCAE grading does not exist for an adverse event, the intensity of mild (1), moderate (2), severe (3), and life-threatening (4) were used.
    Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 380 131 132
    Any On-Study AE
    98.4
    24.4%
    96.9
    70.7%
    97.0
    71.3%
    Severe (>=Grade 3) On-Study AEs
    50.8
    12.6%
    55.0
    40.1%
    52.3
    38.5%
    Serious On-Study AEs
    40.8
    10.1%
    42.0
    30.7%
    39.4
    29%
    Related On-Study AEs
    88.9
    22.1%
    80.2
    58.5%
    78.8
    57.9%
    On-Study AEs Leading to Discontinuation
    9.2
    2.3%
    13.0
    9.5%
    3.8
    2.8%
    AEs with Outcome of Death
    6.1
    1.5%
    9.9
    7.2%
    6.1
    4.5%
    Related AE with Outcome of Death
    2.1
    0.5%
    3.1
    2.3%
    1.5
    1.1%
    15. Secondary Outcome
    Title Percentage of Participants With Immune-Related Adverse Events (irAEs)
    Description An immune related adverse event (irAE) was defined as an adverse event of unknown etiology, associated with study drug exposure and consistent with an immune phenomenon. The irAEs were programmatically determined from a predefined list of MedDRA version 12.0 high-level group terms, high-level terms and preferred terms of all ipilimumab related adverse event. The category of "Other irAEs" includes blood, eye, immune, infections, renal, and respiratory systems.
    Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 380 131 132
    Any On-Study irAEs
    58.2
    14.4%
    61.1
    44.6%
    31.8
    23.4%
    On-Study Severe irAEs
    11.3
    2.8%
    15.3
    11.2%
    3.0
    2.2%
    On-Study Serious irAEs
    10.5
    2.6%
    13.0
    9.5%
    0.8
    0.6%
    On-Study irAEs Leading to Discontinuation
    5.8
    1.4%
    8.4
    6.1%
    0.8
    0.6%
    Death Due to irAEs
    1.3
    0.3%
    1.5
    1.1%
    0
    0%
    Gastrointestinal irAEs (any grade)
    32.1
    8%
    29.0
    21.2%
    14.4
    10.6%
    Severe (>= Grade 3) Gastrointestinal irAEs
    6.3
    1.6%
    7.6
    5.5%
    0.8
    0.6%
    Liver irAEs (any grade)
    2.1
    0.5%
    3.8
    2.8%
    4.5
    3.3%
    Severe (>= Grade 3) Liver irAEs
    1.1
    0.3%
    0.8
    0.6%
    2.3
    1.7%
    Endocrine irAEs (any grade)
    3.9
    1%
    7.6
    5.5%
    1.5
    1.1%
    Severe (>= Grade 3) Endocrine irAEs
    1.1
    0.3%
    3.8
    2.8%
    0
    0%
    Skin irAEs (any grade)
    40.0
    9.9%
    43.5
    31.8%
    16.7
    12.3%
    Severe (>= Grade 3) Skin irAEs
    2.4
    0.6%
    1.5
    1.1%
    0
    0%
    Neurological irAEs (any grade)
    0.5
    0.1%
    0
    0%
    0
    0%
    Severe (>= Grade 3) Neurological irAEs
    0.5
    0.1%
    0
    0%
    0
    0%
    Other irAEs (any grade)
    3.2
    0.8%
    4.6
    3.4%
    2.3
    1.7%
    Severe (>= Grade 3) Other irAEs
    1.6
    0.4%
    2.3
    1.7%
    0.8
    0.6%
    16. Secondary Outcome
    Title Percentage of Participants With Worst On-Study Hematological Abnormalities
    Description ANC=Absolute Neutrophil Count. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
    Time Frame On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication. N=Number of participants analyzed; n=number of participants with given laboratory evaluation.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 380 131 132
    Hemoglobin, Grade 0 (n=352, 121, 126)
    48.9
    12.1%
    44.6
    32.6%
    46.8
    34.4%
    Hemoglobin, Grade 1 (n=352, 121, 126)
    37.2
    9.2%
    40.5
    29.6%
    34.1
    25.1%
    Hemoglobin, Grade 2 (n=352, 121, 126)
    12.2
    3%
    14.0
    10.2%
    15.1
    11.1%
    Hemoglobin, Grade 3 (n=352, 121, 126)
    1.7
    0.4%
    0.8
    0.6%
    4.0
    2.9%
    Hemoglobin, Grade 4 (n=352, 121, 126)
    0
    0%
    0
    0%
    0
    0%
    Hemoglobin, Grade 1-4 (n=352, 121, 126)
    51.1
    12.7%
    55.4
    40.4%
    53.2
    39.1%
    Hemoglobin, Grade 3-4 (n=352, 121, 126)
    1.7
    0.4%
    0.8
    0.6%
    4.0
    2.9%
    White Blood Cells, Grade 0 (n=352, 121, 126)
    97.2
    24.1%
    95.9
    70%
    92.9
    68.3%
    White Blood Cells, Grade 1 (n=352, 121, 126)
    1.4
    0.3%
    1.7
    1.2%
    5.6
    4.1%
    White Blood Cells, Grade 2 (n=352, 121, 126)
    1.1
    0.3%
    2.5
    1.8%
    1.6
    1.2%
    White Blood Cells, Grade 3 (n=352, 121, 126)
    0.3
    0.1%
    0
    0%
    0
    0%
    White Blood Cells, Grade 4 (n=352, 121, 126)
    0
    0%
    0
    0%
    0
    0%
    White Blood Cells, Grade 1-4 (n=352, 121, 126)
    2.8
    0.7%
    4.1
    3%
    7.1
    5.2%
    White Blood Cells, Grade 3-4 (n=352, 121, 126)
    0.3
    0.1%
    0
    0%
    0
    0%
    ANC, Grade 0 (n=352, 121, 126)
    95.5
    23.7%
    93.4
    68.2%
    96.0
    70.6%
    ANC, Grade 1 (n=352, 121, 126)
    2.8
    0.7%
    3.3
    2.4%
    2.4
    1.8%
    ANC, Grade 2 (n=352, 121, 126)
    0.9
    0.2%
    2.5
    1.8%
    0.8
    0.6%
    ANC, Grade 3 (n=352, 121, 126)
    0.6
    0.1%
    0.8
    0.6%
    0.8
    0.6%
    ANC, Grade 4 (n=352, 121, 126)
    0.3
    0.1%
    0
    0%
    0
    0%
    ANC, Grade 1-4 (n=352, 121, 126)
    4.5
    1.1%
    6.6
    4.8%
    4.0
    2.9%
    ANC, Grade 3-4 (n=352, 121, 126)
    0.9
    0.2%
    0.8
    0.6%
    0.8
    0.6%
    Platelet Count, Grade 0 (n=349, 121, 126)
    94.6
    23.5%
    90.1
    65.8%
    91.3
    67.1%
    Platelet Count, Grade 1 (n=349, 121, 126)
    4.9
    1.2%
    9.1
    6.6%
    8.7
    6.4%
    Platelet Count, Grade 2 (n=349, 121, 126)
    0.6
    0.1%
    0.8
    0.6%
    0
    0%
    Platelet Count, Grade 3 (n=349, 121, 126)
    0
    0%
    0
    0%
    0
    0%
    Platelet Count, Grade 4 (n=349, 121, 126)
    0
    0%
    0
    0%
    0
    0%
    Platelet Count, Grade 1-4 (n=349, 121, 126)
    5.4
    1.3%
    9.9
    7.2%
    8.7
    6.4%
    Platelet Count, Grade 3-4 (n=349, 121, 126)
    0
    0%
    0
    0%
    0
    0%
    Lymphocytes (absolute), Grade 0 (n=352, 121, 126)
    33.8
    8.4%
    34.7
    25.3%
    22.2
    16.3%
    Lymphocytes (absolute), Grade 1 (n=352, 121, 126)
    46.3
    11.5%
    47.9
    35%
    42.9
    31.5%
    Lymphocytes (absolute), Grade 2 (n=352, 121, 126)
    15.1
    3.7%
    14.9
    10.9%
    25.4
    18.7%
    Lymphocytes (absolute), Grade 3 (n=352, 121, 126)
    4.3
    1.1%
    2.5
    1.8%
    9.5
    7%
    Lymphocytes (absolute), Grade 4 (n=352, 121, 126)
    0.6
    0.1%
    0
    0%
    0
    0%
    Lymphocytes (absolute), Grade 1-4(n=352, 121, 126)
    66.2
    16.4%
    65.3
    47.7%
    77.8
    57.2%
    Lymphocytes (absolute), Grade 3-4(n=352, 121, 126)
    4.8
    1.2%
    2.5
    1.8%
    9.5
    7%
    17. Secondary Outcome
    Title Percentage of Participants With Worst On-Study Liver Abnormalities
    Description ALT=alanine aminotransferase; AST=aspartate aminotransferase. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
    Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication. N=Number of participants analyzed; n=number of participants with given laboratory evaluation.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 380 131 132
    ALT, Grade 0 (n=352, 121, 126)
    83.2
    20.6%
    76.0
    55.5%
    84.9
    62.4%
    ALT, Grade 1 (n=352, 121, 126)
    13.6
    3.4%
    19.0
    13.9%
    12.7
    9.3%
    ALT, Grade 2 (n=352, 121, 126)
    2.0
    0.5%
    3.3
    2.4%
    1.6
    1.2%
    ALT, Grade 3 (n=352, 121, 126)
    0.9
    0.2%
    1.7
    1.2%
    0.8
    0.6%
    ALT, Grade 4 (n=352, 121, 126)
    0.3
    0.1%
    0
    0%
    0
    0%
    ALT, Grade 1-4 (n=352, 121, 126)
    16.8
    4.2%
    24.0
    17.5%
    15.1
    11.1%
    ALT, Grade 3-4 (n=352, 121, 126)
    1.1
    0.3%
    1.7
    1.2%
    0.8
    0.6%
    AST, Grade 0 (n=352, 121, 126)
    80.4
    20%
    71.9
    52.5%
    81.7
    60.1%
    AST, Grade 1 (n=352, 121, 126)
    16.5
    4.1%
    23.1
    16.9%
    15.1
    11.1%
    AST, Grade 2 (n=352, 121, 126)
    1.4
    0.3%
    3.3
    2.4%
    2.4
    1.8%
    AST, Grade 3 (n=352, 121, 126)
    1.4
    0.3%
    1.7
    1.2%
    0.8
    0.6%
    AST, Grade 4 (n=352, 121, 126)
    0.3
    0.1%
    0
    0%
    0
    0%
    AST, Grade 1-4 (n=352, 121, 126)
    19.6
    4.9%
    28.1
    20.5%
    18.3
    13.5%
    AST, Grade 3-4 (n=352, 121, 126)
    1.7
    0.4%
    1.7
    1.2%
    0.8
    0.6%
    Total Bilirubin, Grade 0 (n=353, 121, 127)
    95.5
    23.7%
    93.4
    68.2%
    98.4
    72.4%
    Total Bilirubin, Grade 1 (n=353, 121, 127)
    2.5
    0.6%
    4.1
    3%
    0.8
    0.6%
    Total Bilirubin, Grade 2 (n=353, 121, 127)
    1.4
    0.3%
    1.7
    1.2%
    0.8
    0.6%
    Total Bilirubin, Grade 3 (n=353, 121, 127)
    0.6
    0.1%
    0.8
    0.6%
    0
    0%
    Total Bilirubin, Grade 4 (n=353, 121, 127)
    0
    0%
    0
    0%
    0
    0%
    Total Bilirubin, Grade 1-4 (n=353, 121, 127)
    4.5
    1.1%
    6.6
    4.8%
    1.6
    1.2%
    Total Bilirubin, Grade 3-4 (n=353, 121, 127)
    0.6
    0.1%
    0.8
    0.6%
    0
    0%
    Alkaline Phosphatase, Grade 0 (n=353, 121, 128)
    73.7
    18.3%
    71.9
    52.5%
    71.1
    52.3%
    Alkaline Phosphatase, Grade 1 (n=353, 121, 128)
    19.8
    4.9%
    20.7
    15.1%
    24.2
    17.8%
    Alkaline Phosphatase, Grade 2 (n=353, 121, 128)
    4.8
    1.2%
    4.1
    3%
    3.9
    2.9%
    Alkaline Phosphatase, Grade 3 (n=353, 121, 128)
    1.7
    0.4%
    3.3
    2.4%
    0.8
    0.6%
    Alkaline Phosphatase, Grade 4 (n=353, 121, 128)
    0
    0%
    0
    0%
    0
    0%
    Alkaline Phosphatase, Grade 1-4 (n=353, 121, 128)
    26.3
    6.5%
    28.1
    20.5%
    28.9
    21.3%
    Alkaline Phosphatase, Grade 3-4 (n=353, 121, 128)
    1.7
    0.4%
    3.3
    2.4%
    0.8
    0.6%
    18. Secondary Outcome
    Title Percentage of Participants With Worst On-Study Renal Abnormalities
    Description CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
    Time Frame On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication. N=Number of participants analyzed; n=number of participants with given laboratory evaluation.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 380 131 132
    Creatinine, Grade 0 (n=353, 121, 128)
    89.5
    22.2%
    88.4
    64.5%
    88.3
    64.9%
    Creatinine, Grade 1 (n=353, 121, 128)
    8.8
    2.2%
    9.9
    7.2%
    9.4
    6.9%
    Creatinine, Grade 2 (n=353, 121, 128)
    1.4
    0.3%
    1.7
    1.2%
    2.3
    1.7%
    Creatinine, Grade 3 (n=353, 121, 128)
    0.3
    0.1%
    0
    0%
    0
    0%
    Creatinine, Grade 4 (n=353, 121, 128)
    0
    0%
    0
    0%
    0
    0%
    Creatinine, Grade 1-4 (n=353, 121, 128)
    10.5
    2.6%
    11.6
    8.5%
    11.7
    8.6%
    Creatinine, Grade 3-4 (n=353, 121, 128)
    0.3
    0.1%
    0
    0%
    0
    0%
    19. Secondary Outcome
    Title Clinically Meaningful Changes in Vital Signs and Physical Examinations
    Description Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.
    Time Frame vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least 1 dose or any partial dose of study medication.
    Arm/Group Title Ipilimumab Plus gp100 Ipilimumab Monotherapy gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    Measure Participants 380 131 132
    Clinically Meaningful Vital Sign Changes
    0
    0%
    0
    0%
    0
    0%
    Clinically Meaningful Physical Examination Changes
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
    Arm/Group Description Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with matching vaccine placebo. The vaccine placebo consisted of sterile 0.9% sodium chloride. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Ipilimumab was administered at a dosage of 3 mg/kg as an intravenous (IV) infusion administered over 90 minutes every 3 weeks for a total of 4 doses, together with gp100. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy. Gp100 consisted of 2 separate peptide components: Peptide A, a peptide with sequence YLEPGPVTV (gp100:280-288[288V]) and Peptide B, a peptide with the sequence IMDQVPFSV (gp100:209-217[210M]). Each peptide was prepared with Montanide ISA-51. One dose of gp100 consisted of the administration of Peptide A, at a dosage of 2 mL or 1 mg, and Peptide B, at a dosage of 2 mL or 1 mg. After Week 12, subjects who met re-induction criteria could receive further cycles of their randomized study therapy.
    All Cause Mortality
    Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 55/131 (42%) 155/380 (40.8%) 52/132 (39.4%)
    Blood and lymphatic system disorders
    ANAEMIA 4/131 (3.1%) 5/380 (1.3%) 5/132 (3.8%)
    HAEMOLYTIC ANAEMIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    LEUKOCYTOSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    NEUTROPENIA 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    THROMBOCYTOPENIA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    Cardiac disorders
    ATRIAL FIBRILLATION 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    CARDIAC FAILURE 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    CARDIAC FAILURE CONGESTIVE 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    CARDIAC TAMPONADE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    CARDIOPULMONARY FAILURE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    CORONARY ARTERY DISEASE 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    PERICARDIAL EFFUSION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    SUPRAVENTRICULAR TACHYCARDIA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    TACHYCARDIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Endocrine disorders
    ADRENAL INSUFFICIENCY 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    HYPOGONADISM 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HYPOPHYSITIS 2/131 (1.5%) 1/380 (0.3%) 0/132 (0%)
    HYPOPITUITARISM 2/131 (1.5%) 3/380 (0.8%) 0/132 (0%)
    HYPOTHYROIDISM 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Eye disorders
    IRIDOCYCLITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    ABDOMINAL PAIN 2/131 (1.5%) 4/380 (1.1%) 5/132 (3.8%)
    ABDOMINAL PAIN UPPER 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    ABDOMINAL WALL MASS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    ASCITES 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    COLITIS 7/131 (5.3%) 14/380 (3.7%) 0/132 (0%)
    CONSTIPATION 0/131 (0%) 3/380 (0.8%) 1/132 (0.8%)
    DIARRHOEA 6/131 (4.6%) 16/380 (4.2%) 0/132 (0%)
    DYSPHAGIA 1/131 (0.8%) 0/380 (0%) 1/132 (0.8%)
    GASTRITIS 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    GASTROINTESTINAL HAEMORRHAGE 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    GASTROINTESTINAL PERFORATION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HAEMATOCHEZIA 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    HAEMORRHOIDS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    ILEUS 0/131 (0%) 3/380 (0.8%) 0/132 (0%)
    INTESTINAL HAEMORRHAGE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    INTESTINAL OBSTRUCTION 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    INTESTINAL PERFORATION 0/131 (0%) 3/380 (0.8%) 0/132 (0%)
    INTUSSUSCEPTION 0/131 (0%) 0/380 (0%) 2/132 (1.5%)
    LARGE INTESTINAL OBSTRUCTION 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    LARGE INTESTINE PERFORATION 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    NAUSEA 2/131 (1.5%) 6/380 (1.6%) 4/132 (3%)
    PERITONITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    PROCTALGIA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    RECTAL STENOSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    SMALL INTESTINAL OBSTRUCTION 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    UPPER GASTROINTESTINAL HAEMORRHAGE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    VOMITING 3/131 (2.3%) 7/380 (1.8%) 3/132 (2.3%)
    General disorders
    ADVERSE EVENT 1/131 (0.8%) 3/380 (0.8%) 0/132 (0%)
    ASTHENIA 3/131 (2.3%) 4/380 (1.1%) 1/132 (0.8%)
    CHEST PAIN 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    CHILLS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    DISEASE PROGRESSION 2/131 (1.5%) 6/380 (1.6%) 3/132 (2.3%)
    FATIGUE 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    GAIT DISTURBANCE 1/131 (0.8%) 0/380 (0%) 1/132 (0.8%)
    GENERAL PHYSICAL HEALTH DETERIORATION 0/131 (0%) 2/380 (0.5%) 2/132 (1.5%)
    GENERALISED OEDEMA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    HERNIA OBSTRUCTIVE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    INFLUENZA LIKE ILLNESS 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    INFUSION RELATED REACTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    INJECTION SITE REACTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    INJECTION SITE ULCER 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    MULTI-ORGAN FAILURE 0/131 (0%) 2/380 (0.5%) 2/132 (1.5%)
    OEDEMA 2/131 (1.5%) 1/380 (0.3%) 0/132 (0%)
    OEDEMA PERIPHERAL 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    PAIN 1/131 (0.8%) 3/380 (0.8%) 0/132 (0%)
    PYREXIA 2/131 (1.5%) 7/380 (1.8%) 1/132 (0.8%)
    Hepatobiliary disorders
    ACUTE HEPATIC FAILURE 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    BILE DUCT OBSTRUCTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    CHOLECYSTITIS 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    HEPATIC FAILURE 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    HEPATITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HYPERBILIRUBINAEMIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    JAUNDICE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    JAUNDICE CHOLESTATIC 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Infections and infestations
    APPENDICITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    BACTERAEMIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    BRONCHOPNEUMONIA 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    CATHETER RELATED INFECTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    CELLULITIS 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    CYSTITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    ENTEROCOCCAL BACTERAEMIA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    ERYSIPELAS 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    EYELID INFECTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    GASTROINTESTINAL INFECTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HEPATITIS A 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    HEPATITIS B 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    INFECTION 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    LOCALISED INFECTION 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    LOWER RESPIRATORY TRACT INFECTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    MENINGITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    PERIRECTAL ABSCESS 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    PNEUMONIA 2/131 (1.5%) 8/380 (2.1%) 3/132 (2.3%)
    POSTOPERATIVE WOUND INFECTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    PSEUDOMONAL SEPSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    SEPSIS 3/131 (2.3%) 4/380 (1.1%) 0/132 (0%)
    SEPTIC SHOCK 1/131 (0.8%) 1/380 (0.3%) 1/132 (0.8%)
    URINARY TRACT INFECTION 0/131 (0%) 2/380 (0.5%) 3/132 (2.3%)
    Injury, poisoning and procedural complications
    ACCIDENTAL OVERDOSE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    FEMORAL NECK FRACTURE 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    GASTROINTESTINAL STOMA COMPLICATION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HIP FRACTURE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    PROCEDURAL COMPLICATION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Investigations
    ASPARTATE AMINOTRANSFERASE INCREASED 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    BLOOD CORTICOTROPHIN DECREASED 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    GAMMA-GLUTAMYLTRANSFERASE INCREASED 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    INTERNATIONAL NORMALISED RATIO ABNORMAL 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    URINE OUTPUT DECREASED 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 2/131 (1.5%) 3/380 (0.8%) 1/132 (0.8%)
    DEHYDRATION 1/131 (0.8%) 8/380 (2.1%) 4/132 (3%)
    FAILURE TO THRIVE 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    HYPOALBUMINAEMIA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    HYPOGLYCAEMIA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    HYPONATRAEMIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HYPOPHAGIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    MALNUTRITION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    TUMOUR LYSIS SYNDROME 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    BACK PAIN 0/131 (0%) 2/380 (0.5%) 2/132 (1.5%)
    BONE PAIN 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    MUSCULAR WEAKNESS 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    MUSCULOSKELETAL PAIN 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    NECK PAIN 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    PAIN IN EXTREMITY 0/131 (0%) 3/380 (0.8%) 1/132 (0.8%)
    PATHOLOGICAL FRACTURE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    POLYMYALGIA RHEUMATICA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    CANCER PAIN 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    INTRACRANIAL TUMOUR HAEMORRHAGE 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    MALIGNANT ASCITES 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    MALIGNANT MELANOMA 0/131 (0%) 3/380 (0.8%) 1/132 (0.8%)
    MALIGNANT NEOPLASM PROGRESSION 0/131 (0%) 3/380 (0.8%) 0/132 (0%)
    METASTASES TO BREAST 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    METASTASES TO CENTRAL NERVOUS SYSTEM 2/131 (1.5%) 3/380 (0.8%) 0/132 (0%)
    METASTASES TO SPINE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    METASTATIC MALIGNANT MELANOMA 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    METASTATIC NEOPLASM 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    METASTATIC PAIN 1/131 (0.8%) 3/380 (0.8%) 0/132 (0%)
    TUMOUR HAEMORRHAGE 0/131 (0%) 1/380 (0.3%) 2/132 (1.5%)
    TUMOUR PAIN 2/131 (1.5%) 2/380 (0.5%) 1/132 (0.8%)
    Nervous system disorders
    APHASIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    ATAXIA 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    BRAIN OEDEMA 1/131 (0.8%) 2/380 (0.5%) 0/132 (0%)
    CEREBRAL HAEMORRHAGE 0/131 (0%) 0/380 (0%) 2/132 (1.5%)
    CEREBROVASCULAR ACCIDENT 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    COMA 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    CONVULSION 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    DEPRESSED LEVEL OF CONSCIOUSNESS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    DIZZINESS 0/131 (0%) 0/380 (0%) 2/132 (1.5%)
    DYSARTHRIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    EPIDURITIS 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    GUILLAIN-BARRE SYNDROME 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HAEMORRHAGE INTRACRANIAL 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    HEADACHE 0/131 (0%) 2/380 (0.5%) 1/132 (0.8%)
    HYDROCEPHALUS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HYPOAESTHESIA 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    INTRACRANIAL PRESSURE INCREASED 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    LETHARGY 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    MENINGEAL DISORDER 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    MYOCLONUS 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    SPINAL CORD COMPRESSION 1/131 (0.8%) 3/380 (0.8%) 0/132 (0%)
    SYNCOPE 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    Psychiatric disorders
    ANXIETY 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    CONFUSIONAL STATE 2/131 (1.5%) 1/380 (0.3%) 1/132 (0.8%)
    DELIRIUM 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    MENTAL STATUS CHANGES 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    Renal and urinary disorders
    ATONIC URINARY BLADDER 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    BLADDER PAIN 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    GLOMERULONEPHRITIS 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    HYDRONEPHROSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    RENAL FAILURE 3/131 (2.3%) 3/380 (0.8%) 0/132 (0%)
    RENAL FAILURE ACUTE 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    RENAL TUBULAR NECROSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    URETERIC OBSTRUCTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    URINARY INCONTINENCE 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    URINARY RETENTION 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    Reproductive system and breast disorders
    BREAST MASS 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    PELVIC PAIN 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Respiratory, thoracic and mediastinal disorders
    ACUTE PULMONARY OEDEMA 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    ACUTE RESPIRATORY DISTRESS SYNDROME 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    BRONCHIAL OBSTRUCTION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    COUGH 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    DYSPNOEA 3/131 (2.3%) 2/380 (0.5%) 7/132 (5.3%)
    HAEMOPTYSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    HAEMOTHORAX 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    PAINFUL RESPIRATION 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    PLEURAL EFFUSION 2/131 (1.5%) 5/380 (1.3%) 4/132 (3%)
    PLEURITIC PAIN 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    PNEUMONITIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    PULMONARY EMBOLISM 1/131 (0.8%) 3/380 (0.8%) 2/132 (1.5%)
    PULMONARY HAEMORRHAGE 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    RESPIRATORY ARREST 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    RESPIRATORY DEPRESSION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    RESPIRATORY FAILURE 1/131 (0.8%) 2/380 (0.5%) 0/132 (0%)
    SLEEP APNOEA SYNDROME 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    Skin and subcutaneous tissue disorders
    LEUKOCYTOCLASTIC VASCULITIS 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    RASH 0/131 (0%) 2/380 (0.5%) 0/132 (0%)
    RASH GENERALISED 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    RASH PRURITIC 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    TOXIC EPIDERMAL NECROLYSIS 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    Vascular disorders
    ANGIOPATHY 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    ARTERIAL THROMBOSIS LIMB 1/131 (0.8%) 0/380 (0%) 0/132 (0%)
    DEEP VEIN THROMBOSIS 2/131 (1.5%) 5/380 (1.3%) 1/132 (0.8%)
    HAEMATOMA 0/131 (0%) 1/380 (0.3%) 1/132 (0.8%)
    HYPERTENSIVE CRISIS 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    HYPOTENSION 3/131 (2.3%) 1/380 (0.3%) 2/132 (1.5%)
    LYMPHOEDEMA 0/131 (0%) 0/380 (0%) 1/132 (0.8%)
    SUPERIOR VENA CAVAL OCCLUSION 0/131 (0%) 1/380 (0.3%) 0/132 (0%)
    THROMBOSIS 1/131 (0.8%) 1/380 (0.3%) 0/132 (0%)
    Other (Not Including Serious) Adverse Events
    Ipilimumab Monotherapy Ipilimumab Plus gp100 gp100
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 124/131 (94.7%) 362/380 (95.3%) 124/132 (93.9%)
    Blood and lymphatic system disorders
    ANAEMIA 14/131 (10.7%) 36/380 (9.5%) 22/132 (16.7%)
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 0/131 (0%) 13/380 (3.4%) 9/132 (6.8%)
    ABDOMINAL PAIN 20/131 (15.3%) 64/380 (16.8%) 18/132 (13.6%)
    ABDOMINAL PAIN UPPER 7/131 (5.3%) 17/380 (4.5%) 11/132 (8.3%)
    CONSTIPATION 27/131 (20.6%) 79/380 (20.8%) 34/132 (25.8%)
    DIARRHOEA 41/131 (31.3%) 142/380 (37.4%) 26/132 (19.7%)
    DYSPEPSIA 2/131 (1.5%) 14/380 (3.7%) 10/132 (7.6%)
    FLATULENCE 3/131 (2.3%) 9/380 (2.4%) 8/132 (6.1%)
    NAUSEA 44/131 (33.6%) 127/380 (33.4%) 49/132 (37.1%)
    VOMITING 30/131 (22.9%) 71/380 (18.7%) 27/132 (20.5%)
    General disorders
    ADVERSE EVENT 4/131 (3.1%) 22/380 (5.8%) 5/132 (3.8%)
    ASTHENIA 6/131 (4.6%) 37/380 (9.7%) 17/132 (12.9%)
    CHILLS 9/131 (6.9%) 23/380 (6.1%) 7/132 (5.3%)
    FATIGUE 55/131 (42%) 137/380 (36.1%) 41/132 (31.1%)
    INFLUENZA LIKE ILLNESS 7/131 (5.3%) 20/380 (5.3%) 3/132 (2.3%)
    INJECTION SITE ERYTHEMA 1/131 (0.8%) 26/380 (6.8%) 5/132 (3.8%)
    INJECTION SITE INDURATION 0/131 (0%) 25/380 (6.6%) 4/132 (3%)
    INJECTION SITE PAIN 2/131 (1.5%) 25/380 (6.6%) 13/132 (9.8%)
    INJECTION SITE REACTION 2/131 (1.5%) 109/380 (28.7%) 26/132 (19.7%)
    OEDEMA PERIPHERAL 12/131 (9.2%) 47/380 (12.4%) 22/132 (16.7%)
    PAIN 6/131 (4.6%) 23/380 (6.1%) 15/132 (11.4%)
    PYREXIA 15/131 (11.5%) 74/380 (19.5%) 23/132 (17.4%)
    Infections and infestations
    URINARY TRACT INFECTION 8/131 (6.1%) 8/380 (2.1%) 4/132 (3%)
    Investigations
    WEIGHT DECREASED 8/131 (6.1%) 33/380 (8.7%) 12/132 (9.1%)
    Metabolism and nutrition disorders
    DECREASED APPETITE 33/131 (25.2%) 85/380 (22.4%) 29/132 (22%)
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 12/131 (9.2%) 30/380 (7.9%) 14/132 (10.6%)
    BACK PAIN 9/131 (6.9%) 32/380 (8.4%) 16/132 (12.1%)
    MUSCULOSKELETAL CHEST PAIN 7/131 (5.3%) 7/380 (1.8%) 2/132 (1.5%)
    MUSCULOSKELETAL PAIN 5/131 (3.8%) 30/380 (7.9%) 10/132 (7.6%)
    MYALGIA 8/131 (6.1%) 28/380 (7.4%) 4/132 (3%)
    PAIN IN EXTREMITY 9/131 (6.9%) 51/380 (13.4%) 19/132 (14.4%)
    Nervous system disorders
    DIZZINESS 5/131 (3.8%) 27/380 (7.1%) 13/132 (9.8%)
    HEADACHE 19/131 (14.5%) 64/380 (16.8%) 18/132 (13.6%)
    Psychiatric disorders
    ANXIETY 5/131 (3.8%) 31/380 (8.2%) 9/132 (6.8%)
    INSOMNIA 16/131 (12.2%) 33/380 (8.7%) 15/132 (11.4%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 21/131 (16%) 55/380 (14.5%) 17/132 (12.9%)
    DYSPNOEA 16/131 (12.2%) 45/380 (11.8%) 20/132 (15.2%)
    Skin and subcutaneous tissue disorders
    ERYTHEMA 10/131 (7.6%) 26/380 (6.8%) 7/132 (5.3%)
    HYPERHIDROSIS 6/131 (4.6%) 14/380 (3.7%) 12/132 (9.1%)
    PRURITUS 39/131 (29.8%) 79/380 (20.8%) 14/132 (10.6%)
    RASH 29/131 (22.1%) 78/380 (20.5%) 9/132 (6.8%)
    Vascular disorders
    HOT FLUSH 6/131 (4.6%) 8/380 (2.1%) 8/132 (6.1%)
    HYPOTENSION 8/131 (6.1%) 12/380 (3.2%) 4/132 (3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title BMS Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00094653
    Other Study ID Numbers:
    • MDX010-20
    • CA184-002
    First Posted:
    Oct 22, 2004
    Last Update Posted:
    Jul 11, 2011
    Last Verified:
    Jun 1, 2011