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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094653
• Other study ID #: MDX010-20
• Secondary ID: CA184-002
• Status: Completed
• Phase: Phase 3
• First received: October 21, 2004
• Last updated: June 29, 2011
• Start date: September 2004
• Est. completion date: October 2009

Study information

• Verified date: June 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1783
• Est. completion date: October 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Metastases

Intervention

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

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.

Locations

Country	Name	City	State
Argentina	Hospital Militar Central	Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad de Buenos Aires
Argentina	Hospital General de Agudos Carlos G. Durand	Ciudad de Buenos Aires
Argentina	Hospital Militar Central	Ciudad de Buenos Aires
Argentina	Hospital Municipal de Oncoligia Maria Curie	Ciudad de Buenos Aires	Buenos Aires
Argentina	Hospital Municipal de Oncologia Maria Curie	Ciudad de Buenos Aires
Argentina	Instituto Alexander Fleming	Ciudad de Buenos Aires
Argentina	Instituto de Oncologia Angel H. Roffo	Ciudad de Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba S.A.	Cordoba
Argentina	Hospital Privado de Cordoba S.A.	Cordoba
Argentina	Instituto Medico Platense	La Plata	Provincia de Buenos Aires
Argentina	ISIS Clinica Especializada	Santa Fe
Argentina	ISIS Clinica Especializada	Santa Fe
Belgium	Erasme Hospital	Brussels
Belgium	Erasme Hospital, Free Universtiy of Brussels	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	U.Z. Gent	Gent
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven
Belgium	Cliniques Universitaires UCL de Mont-Godinne	Yvoir
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospital de Cancer de Barretos - Fundacao Pio XII	Barretos - SP
Brazil	Biocor - Hosp. de Doencas Cardiovasculares Ltda.	Belo Horizonte - MG
Brazil	Hospital Araujo Jorge da Associacoa de Combate ao Cancer em Goias	Goiania	GO
Brazil	Hospital Araujo Jorge	Goiania - GO
Brazil	Fundacoa Hospital Amaral Carvalho	Jau	SP
Brazil	Pro Onco Centro Tratamento Oncologico	Londrina	PR
Brazil	Pro Onco Centro Tratemento Oncologico	Londrina - PR
Brazil	Fundacao Central Sul-Americana para o Desenvolvimento de Drogas Anticancer-SOAD	Porto Alegre
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre	RS
Brazil	Fund. SOAD / HC de Porto Alegre	Porto Alegre - RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre - RS
Brazil	Santo Andre Diagnosticos aTratamentos	Santo Andre	SP
Brazil	Santo Andre Diagnosticos e Tratamentos Ltda.	Santo Andre-SP
Brazil	Sociedade Beneficante de Sennores - Hospital Sino Libante	Sao Paulo	SP
Brazil	HC-FMUSP	Sao Paulo - SP
Brazil	Hospital Sirio Labanes	Sao Paulo-SP
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Cancer Centre of Southeastern Ontario at KGH	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Sir Mortimer B. Davis - Jewish General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital Regional Cancer Centre	Ottawa	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Chile	Instituto Nacional del Cancer	Independencia	Santiago
Chile	Clinica Davila	Recoleta	Santiago
Chile	Clinica Renaca	Renaca	Vina Del Mar
Chile	Fundacion Arturo Lopez Perez	Santiago
Chile	Hospital Barros Luco	Santiago
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Hopital Sainte-Marguerite	Marseille
France	Hopital Saint-Eloi	Montpellier
France	Hotel Dieu	Nantes
France	Centre Antoine Lacassagne	Nice cedex 2
France	Hopital Saint-Louis	Paris
France	Centre Eugene Marquis	Rennes
France	Centre-Hospitalier Universitaire de Saint-Etienne	Saint-Etienne
France	Centre Alexis Vautrin	Vandoeuvre les Nancy
France	Institut Gustave Roussy (IGR)	Villejuif
Germany	Klinikum Augsburg	Augsburg
Germany	Charite Universitaets medizin Berlin	Berlin
Germany	Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Dusseldorf	Duesseldorf
Germany	Universitaetsklinikum Erlangen	Erlangen
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Heidelberg	Heidelburg
Germany	Klinik fur und Poliklinik fur Dermatologie, Venerologie und Allergologie	Hufelandstr. 55	Essen
Germany	Klinikum der Friedrich-Schiller-Universitaet Jena	Jena
Germany	Klinikum Mannheim gGmbH	Mannheim
Germany	University of Mannheim	Mannheim
Germany	Klinikum Rechts der Isar / TU Muenchen	Muenchen
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Hungary	National Institute of Oncology	Budapest
Hungary	University of Debrecen, Medical and Health Sciences Center	Debrecen
Hungary	Semmelweis Hospital	Miskolc
Hungary	University of Szeged, Albert Szent-Gyorgyi Medical and Pharmaceutical Center	Szeged
Netherlands	Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum (VUMC)	Amsterdam
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
South Africa	Mary Potter Oncology Centre	Groenkloof
South Africa	GVI Oncology	Panorama
South Africa	Mary Potter Oncology Centre	Pretoria
South Africa	Sandton Onocology Medical Research	Sandton
Switzerland	Centre Hospitalier Universitaire Vaudois - CHUV	Lausanne	Rue du Bugnon 46
Switzerland	Centre Hospitalier Universitaire Vaudois - CHUV	Lausanne
Switzerland	Dermatologische Klinik Universitatsspital Zurich	Zurich
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	St. Luke's Cancer Center, The Royal Surrey County Hospital	Guildford	Surry
United Kingdom	Christie Hospital	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Poole Hospital	Poole
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Southampton General	Southampton
United States	New Mexico Oncology Hematology Consultants, Ltd.	Albuquerque	New Mexico
United States	Arlington Cancer Center	Arlington	Texas
United States	Emory University Hospital-Winship Cancer Institute	Atlanta	Georgia
United States	Anschutz Cancer Pavilion	Aurora	Colorado
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Family Cancer Center	Bartlett	Tennessee
United States	Beth Isreal Dec Medical Center	Boston	Massachusetts
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers	Boulder	Colorado
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The Christ Hospital Cancer Center	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Family Cancer Center	Collierville	Tennessee
United States	Rocky Mountain Cancer Centers	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center	Columbia	Missouri
United States	Humphrey Cancer Center	Coon Rapids	Minnesota
United States	Center for Oncology Research and Treatment	Dallas	Texas
United States	Henry Ford Medical Center	Dearborn	Michigan
United States	Cancer Care Specialists of Central IL	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	University of Colorado Hospital	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Cancer Centers of the Carolinas	Easley	South Carolina
United States	Hematology-Oncology Associates of CNY	East Syracuse	New York
United States	Cancer Care Specialists of Central IL	Effingham	Illinois
United States	San Diego Cancer Center	Encinitas	California
United States	Humphrey Cancer Center	Fridley	Minnesota
United States	Center for Cancer Care at Goshen Health System	Goshen	Indiana
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Regional Cancer Center	Hollywood	Florida
United States	American Health Network of IN, LLC	Indianapolis	Indiana
United States	Indiana Oncology Hematology Consultants North	Indianapolis	Indiana
United States	Indiana Oncology Hematology South	Indianapolis	Indiana
United States	Shands Jacksonville	Jacksonville	Florida
United States	University of Florida/Jacksonville Faculty Clinic	Jacksonville	Florida
United States	La Jolla Hematology and Oncology Medical Group	La Jolla	California
United States	Moores UCSD Cancer Center	La Jolla	California
United States	Scripps Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Centers	Lakewood	Colorado
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	Rocky Mountain Cancer Centers	Lone Tree	Colorado
United States	Pacific Shores Medical Group	Long Beach	California
United States	Rocky Mountain Cancer Centers	Longmont	Colorado
United States	Cancer Institute Medical Group, Inc	Los Angeles	California
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Norton Hospital	Louisville	Kentucky
United States	University of Louisville Hospital	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Lutherville	Maryland
United States	Cardinal Bernardin Cancer Center, Loyola Unv. Med. Ctr.	Maywood	Illinois
United States	Family Cancer Center	Memphis	Tennessee
United States	The West Clinic	Memphis	Tennessee
United States	Jackson Memorial Hospital & Clinics	Miami	Florida
United States	University of Miami Hospital & Clinics	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Hematology-Oncology Associates of Northern NJ, PA	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	The Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University School of Medicine - Oncology Outpatient Clinic	New Haven	Connecticut
United States	Columbia University Medical Center, Irving Center for Clinical Research	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Indiana Oncology Hematology Consutants of Noblesville	Noblesville	Indiana
United States	North County Oncology Medical Clinical, Inc.	Oceanside	California
United States	Family Cancer Center	Olive Branch	Mississippi
United States	M.D. Anderson Cancer Center Orlando	Orlando	Florida
United States	Palm Beach Cancer Institute	Palm Beach Gardens	Florida
United States	City of Hope Medical Group	Pasadena	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hosptital	Philadelphia	Pennsylvania
United States	Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Hillman Cancer Research Pavilion	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	The Oregon Clinical	Portland	Oregon
United States	Center for Oncology Research and Treatment	Richardson	Texas
United States	Hubert H Humphrey Cancer Center	Robbinsdale	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of California, San Diego	San Diego	California
United States	St. Mary's Medical Center - Northern California Melanoma Center	San Francisco	California
United States	Cancer Institute Medical Group, Inc	Santa Monica	California
United States	Cancer Centers of the Carolinas	Seneca	South Carolina
United States	Cancer Centers of the Carolinas	Spartanburg	South Carolina
United States	St. Joseph Oncology, Inc	St. Joseph	Missouri
United States	Barnes Jewish Hospital	St. Louis	Missouri
United States	Washington Unv. School of Med./ Siteman Cancer Center	St. Louis	Missouri
United States	Overlook Oncology Center	Summit	New Jersey
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona
United States	University Medical Center	Tucson	Arizona
United States	San Diego Cancer Center	Vista	California
United States	Palm Beach Cancer Institute	Wellington	Florida
United States	Henry Ford Medical Center- West Bloomfield	West Bloomfield	Michigan
United States	Palm Beach Cancer Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  France,  Germany,  Hungary,  Netherlands,  South Africa,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)	No
Secondary	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	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.	From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)	No
Secondary	12-, 18-, and 24-Month Survival Rates	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.	Month 12, Month 18, Month 24	No
Secondary	Progression Free Survival (PFS)	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.	From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)	No
Secondary	Percentage of Participants With Progression Free Survival (PFS) at Week 12 and 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.	Week 12, Week 24	No
Secondary	Time to Progression (TTP)	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.	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])	No
Secondary	Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)	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.	BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.	No
Secondary	Determination of Best Overall Response Rate (BORR)	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.	Up to week 24	No
Secondary	Time to Response	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.	From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)	No
Secondary	Duration of Response	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).	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])	No
Secondary	Disease Control Rate (DCR)	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.	Up to week 24	No
Secondary	Delayed Response (Response Beyond Week 24)	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.	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])	No
Secondary	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	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).	Baseline (Day 1, Cycle1), Week 12	No
Secondary	Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death	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.	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]).	Yes
Secondary	Percentage of Participants With Immune-Related Adverse Events (irAEs)	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.	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]).	Yes
Secondary	Percentage of Participants With Worst On-Study Hematological Abnormalities	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.	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]).	Yes
Secondary	Percentage of Participants With Worst On-Study Liver Abnormalities	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.	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]).	Yes
Secondary	Percentage of Participants With Worst On-Study Renal Abnormalities	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.	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]).	Yes
Secondary	Clinically Meaningful Changes in Vital Signs and Physical Examinations	Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.	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	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm