Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 12 of 519 for:    melanoma phase III

Phase 3 Trial in Subjects With Metastatic Melanoma Comparing 3 mg/kg Ipilimumab Versus 10 mg/kg Ipilimumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01515189
Recruitment Status : Completed
First Posted : January 24, 2012
Results First Posted : March 24, 2017
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Melanoma
Intervention Biological: Ipilimumab
Enrollment 831
Recruitment Details  
Pre-assignment Details 831 participants were enrolled; 727 were randomized to a treatment group; 726 received at least one dose of study treatment. Of the 105 participants not treated, 81 no longer met study criteria, 11 withdrew consent, 4 suffered an Adverse Event, 4 died, and 5 were not treated due to investigator decision or other reasons.
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Period Title: Induction
Started 365 [1] 362
Completed 128 130
Not Completed 237 232
Reason Not Completed
Disease Progression             109             155
Study drug toxicity             86             36
Death             24             17
Adverse Event             14             9
Withdrawal by Subject             3             9
No longer meets study criteria             0             2
Lost to Follow-up             1             0
Other             0             4
[1]
Includes 1 subject who was randomized but not treated due to an Adverse Event before treatment
Period Title: First Re-Induction Phase
Started 23 32
Completed 9 17
Not Completed 14 15
Reason Not Completed
Disease progression             6             14
Study drug toxicity             5             0
Withdrawal by Subject             1             1
No longer meets study criteria             1             0
Other             1             0
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg) Total
Hide Arm/Group Description Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity Total of all reporting groups
Overall Number of Baseline Participants 365 362 727
Hide Baseline Analysis Population Description
All randomized participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 365 participants 362 participants 727 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
224
  61.4%
208
  57.5%
432
  59.4%
>=65 years
141
  38.6%
154
  42.5%
295
  40.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 365 participants 362 participants 727 participants
58.6  (14.52) 60.7  (13.22) 59.7  (13.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 365 participants 362 participants 727 participants
Female
146
  40.0%
131
  36.2%
277
  38.1%
Male
219
  60.0%
231
  63.8%
450
  61.9%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median and associated 2-sided 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.
Time Frame Approximately 48 months (assessed up to February 2016)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Median (95% Confidence Interval)
Unit of Measure: months
15.70
(11.63 to 17.84)
11.53
(9.86 to 13.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab (10 mg/kg), Ipilimumab (3 mg/kg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0400
Comments Analysis stratified by ECOG performance status (0 vs. 1), prior treatment for metastatic melanoma (yes vs. no) and M-stage (M0/M1a/M1b vs. M1c without brain metastases vs. M1c with brain metastases).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.70 to 0.99
Estimation Comments Hazard of 10 mg/kg ipilimumab over hazard of 3 mg/kg, with 2-sided 95% confidence intervals are based on a Cox proportional hazards model
2.Secondary Outcome
Title Progression Free Survival (PFS) by mWHO Criteria
Hide Description PFS was defined as the time between randomization date and the date of progression or death, whichever occurred first. A participant who died without reported prior progression was considered to have progressed on the date of death. For a participant who underwent resection post randomization, PFS was censored on last tumor assessment date prior to resection. For those who remained alive and had not progressed, PFS was censored on last evaluable tumor assessment date. Participants who had not died and had no recorded post-baseline tumor assessment were censored at the day of randomization. For participants who had Progressive Disease (PD) prior to Week 12 and a subsequent assessment of Stable Disease (SD), Partial Response (PR), or Complete Response (CR), the date of PD following response was used in the analysis of PFS; otherwise these participants were censored on the date of their last tumor assessment. Median and 2-sided 95% CIs were calculated with Brookmeyer Crowley method.
Time Frame From date of randomization until 540 death events occurred (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Median (95% Confidence Interval)
Unit of Measure: months
2.83
(2.79 to 2.99)
2.79
(2.76 to 2.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab (10 mg/kg), Ipilimumab (3 mg/kg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1548
Comments Analysis stratified by ECOG performance status (0 vs. 1), prior treatment for metastatic melanoma (yes vs. no) and M-stage (M0/M1a/M1b vs. M1c without brain metastases vs. M1c with brain metastases).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.76 to 1.04
Estimation Comments Hazard of 10 mg/kg ipilimumab over hazard of 3 mg/kg, with 2-sided 95% confidence intervals are based on a Cox proportional hazards model
3.Secondary Outcome
Title Best Overall Response Rate (BORR) by mWHO Criteria
Hide Description BORR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR or PR, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for BOR, e.g. on account of missing or “not evaluable” assessments, was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the BORR endpoint). 95% 2-sided exact confidence intervals were computed using the method of Clopper and Pearson.
Time Frame From date of randomization until 540 death events occurred (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants with BORR
15.3
(11.8 to 19.5)
12.2
(9.0 to 16.0)
4.Secondary Outcome
Title Disease Control Rate (DCR) by mWHO Criteria
Hide Description DCR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR, PR or SD, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for Disease Control (DC), (e.g. on account of missing or “not evaluable” assessments), was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the DCR endpoint). 95% 2-sided exact confidence intervals were computed using the Clopper and Pearson method.
Time Frame From date of randomization until 540 death events occurred (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants with DC
31.5
(26.8 to 36.5)
27.9
(23.3 to 32.8)
5.Secondary Outcome
Title Duration of Response (DOR) by mWHO Criteria
Hide Description Duration of response for participants whose BOR was CR or PR was defined as the time between the date measurement criteria were first met for overall response of PR or CR (whichever status was recorded first) and the date of disease progression or death (whichever occurred first). For participants who underwent tumor resection following response but prior to disease progression, duration of response was censored on the date of last evaluable tumor assessment prior to resection. For participants who had BOR of SD, PR or CR at Week 12, or a confirmed response of PR or CR before Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of response. For those participants who remained alive and had not progressed following response, duration of response was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer Crowley method.
Time Frame From date of randomization until 540 death events occurred (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Median (95% Confidence Interval)
Unit of Measure: months
16.33
(5.98 to 23.98)
15.90 [1] 
(10.35 to NA)
[1]
The upper 95% CI for DOR was not reached.
6.Secondary Outcome
Title Duration of Stable Disease by mWHO Criteria
Hide Description Duration of stable disease was defined for participants whose BOR was SD as the time between when SD was first documented and the date of PD or death (whichever occurred first). For a participant who underwent tumor resection following Week 12 but prior to disease progression, duration of stable disease was censored on the date of the last evaluable tumor assessment prior to resection. For participants who had BOR of SD at Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of stable disease. For participants with BOR of SD who had not subsequently progressed and who remained alive, duration of stable disease was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Time Frame From date of randomization until 540 death events occurred (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Median (95% Confidence Interval)
Unit of Measure: months
5.55
(3.02 to 8.02)
3.19
(2.73 to 5.55)
7.Secondary Outcome
Title Rate of Overall Survival
Hide Description OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Survival rates were calculated based on Kaplan-Meier estimation with log-log transformed confidence intervals. The survival rate at x year(s) is defined as the probability that a subject is alive at x year(s) following randomization.
Time Frame Approximately 66 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 365 362
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Survival rate at 1 year
54.28
(49.01 to 59.25)
47.62
(42.35 to 52.70)
Survival rate at 2 years
38.46
(33.44 to 43.45)
30.97
(26.21 to 35.84)
Survival rate at 3 years
31.16
(26.44 to 35.98)
23.15
(18.88 to 27.69)
Survival rate at 4 years
26.63
(22.17 to 31.28)
20.25
(16.21 to 24.62)
Survival rate at 5 years
24.90
(20.54 to 29.48)
18.78
(14.87 to 23.05)
8.Secondary Outcome
Title Overall Survival of Participants With Brain Metastases at Baseline
Hide Description OS for each participant with brain metastases at baseline was measured as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median OS, and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Time Frame From date of randomization until 540 death events occurred (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with brain metastases at baseline
Arm/Group Title Ipilimumab (10 mg/kg) Ipilimumab (3 mg/kg)
Hide Arm/Group Description:
Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses or until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed 65 62
Median (95% Confidence Interval)
Unit of Measure: months
7.00
(3.98 to 12.78)
5.67
(4.21 to 6.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab (10 mg/kg), Ipilimumab (3 mg/kg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.49 to 1.04
Estimation Comments Hazard of 10 mg/kg ipilimumab over hazard of 3 mg/kg. Based on an unstratified Cox proportional hazards model for subset of participants with brain metastases.
Time Frame From Day 1 of study treatment until 90 days following last day of study treatment, up to study completion (August 2017)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 10 MG/KG IPILIMUMAB 3 MG/KG IPILIMUMAB
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
10 MG/KG IPILIMUMAB 3 MG/KG IPILIMUMAB
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
10 MG/KG IPILIMUMAB 3 MG/KG IPILIMUMAB
Affected / at Risk (%) Affected / at Risk (%)
Total   245/364 (67.31%)   194/362 (53.59%) 
Blood and lymphatic system disorders     
Anaemia  1  5/364 (1.37%)  4/362 (1.10%) 
Bicytopenia  1  1/364 (0.27%)  0/362 (0.00%) 
Disseminated intravascular coagulation  1  1/364 (0.27%)  0/362 (0.00%) 
Febrile neutropenia  1  1/364 (0.27%)  0/362 (0.00%) 
Pancytopenia  1  1/364 (0.27%)  0/362 (0.00%) 
Thrombocytopenia  1  1/364 (0.27%)  1/362 (0.28%) 
Cardiac disorders     
Atrial fibrillation  1  3/364 (0.82%)  0/362 (0.00%) 
Cardiac arrest  1  1/364 (0.27%)  0/362 (0.00%) 
Cardiac failure  1  1/364 (0.27%)  0/362 (0.00%) 
Cardiac failure congestive  1  1/364 (0.27%)  0/362 (0.00%) 
Cardio-respiratory arrest  1  0/364 (0.00%)  1/362 (0.28%) 
Myocardial infarction  1  0/364 (0.00%)  2/362 (0.55%) 
Pericardial effusion  1  1/364 (0.27%)  1/362 (0.28%) 
Pericarditis  1  1/364 (0.27%)  0/362 (0.00%) 
Supraventricular tachycardia  1  2/364 (0.55%)  0/362 (0.00%) 
Tachycardia  1  1/364 (0.27%)  0/362 (0.00%) 
Congenital, familial and genetic disorders     
Carney complex  1  1/364 (0.27%)  0/362 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  2/364 (0.55%)  0/362 (0.00%) 
Adrenocortical insufficiency acute  1  2/364 (0.55%)  1/362 (0.28%) 
Adrenocorticotropic hormone deficiency  1  2/364 (0.55%)  2/362 (0.55%) 
Autoimmune thyroiditis  1  1/364 (0.27%)  0/362 (0.00%) 
Diabetes insipidus  1  1/364 (0.27%)  0/362 (0.00%) 
Endocrine disorder  1  1/364 (0.27%)  0/362 (0.00%) 
Hyperthyroidism  1  1/364 (0.27%)  0/362 (0.00%) 
Hypophysitis  1  16/364 (4.40%)  9/362 (2.49%) 
Hypopituitarism  1  5/364 (1.37%)  3/362 (0.83%) 
Hypothalamo-pituitary disorder  1  0/364 (0.00%)  1/362 (0.28%) 
Hypothyroidism  1  0/364 (0.00%)  1/362 (0.28%) 
Lymphocytic hypophysitis  1  1/364 (0.27%)  2/362 (0.55%) 
Thyroiditis  1  2/364 (0.55%)  0/362 (0.00%) 
Thyrotoxic crisis  1  0/364 (0.00%)  1/362 (0.28%) 
Eye disorders     
Eye pain  1  1/364 (0.27%)  0/362 (0.00%) 
Periorbital oedema  1  0/364 (0.00%)  1/362 (0.28%) 
Gastrointestinal disorders     
Abdominal pain  1  1/364 (0.27%)  2/362 (0.55%) 
Abdominal pain upper  1  2/364 (0.55%)  0/362 (0.00%) 
Ascites  1  2/364 (0.55%)  3/362 (0.83%) 
Autoimmune colitis  1  4/364 (1.10%)  4/362 (1.10%) 
Autoimmune pancreatitis  1  1/364 (0.27%)  0/362 (0.00%) 
Colitis  1  33/364 (9.07%)  13/362 (3.59%) 
Colitis ulcerative  1  2/364 (0.55%)  1/362 (0.28%) 
Constipation  1  1/364 (0.27%)  3/362 (0.83%) 
Diarrhoea  1  42/364 (11.54%)  22/362 (6.08%) 
Gastritis  1  3/364 (0.82%)  0/362 (0.00%) 
Gastrointestinal haemorrhage  1  0/364 (0.00%)  2/362 (0.55%) 
Gastrointestinal perforation  1  0/364 (0.00%)  1/362 (0.28%) 
Haematochezia  1  0/364 (0.00%)  1/362 (0.28%) 
Haemorrhagic ascites  1  0/364 (0.00%)  1/362 (0.28%) 
Hiatus hernia  1  0/364 (0.00%)  1/362 (0.28%) 
Intestinal obstruction  1  0/364 (0.00%)  1/362 (0.28%) 
Intestinal perforation  1  2/364 (0.55%)  0/362 (0.00%) 
Large intestinal obstruction  1  0/364 (0.00%)  1/362 (0.28%) 
Large intestine perforation  1  1/364 (0.27%)  1/362 (0.28%) 
Nausea  1  2/364 (0.55%)  3/362 (0.83%) 
Pancreatitis  1  2/364 (0.55%)  0/362 (0.00%) 
Rectal haemorrhage  1  1/364 (0.27%)  0/362 (0.00%) 
Retroperitoneal haematoma  1  1/364 (0.27%)  0/362 (0.00%) 
Retroperitoneal haemorrhage  1  1/364 (0.27%)  0/362 (0.00%) 
Small intestinal haemorrhage  1  0/364 (0.00%)  1/362 (0.28%) 
Small intestinal obstruction  1  1/364 (0.27%)  1/362 (0.28%) 
Small intestinal perforation  1  0/364 (0.00%)  1/362 (0.28%) 
Vomiting  1  3/364 (0.82%)  3/362 (0.83%) 
General disorders     
Asthenia  1  2/364 (0.55%)  2/362 (0.55%) 
Chest pain  1  1/364 (0.27%)  2/362 (0.55%) 
Death  1  1/364 (0.27%)  0/362 (0.00%) 
Fatigue  1  5/364 (1.37%)  1/362 (0.28%) 
General physical health deterioration  1  10/364 (2.75%)  12/362 (3.31%) 
Generalised oedema  1  0/364 (0.00%)  1/362 (0.28%) 
Hyperthermia  1  2/364 (0.55%)  0/362 (0.00%) 
Influenza like illness  1  1/364 (0.27%)  0/362 (0.00%) 
Multiple organ dysfunction syndrome  1  1/364 (0.27%)  1/362 (0.28%) 
Oedema  1  1/364 (0.27%)  0/362 (0.00%) 
Pain  1  1/364 (0.27%)  5/362 (1.38%) 
Performance status decreased  1  0/364 (0.00%)  1/362 (0.28%) 
Peripheral swelling  1  0/364 (0.00%)  1/362 (0.28%) 
Pyrexia  1  9/364 (2.47%)  5/362 (1.38%) 
Ulcer haemorrhage  1  1/364 (0.27%)  0/362 (0.00%) 
Hepatobiliary disorders     
Acute hepatic failure  1  1/364 (0.27%)  0/362 (0.00%) 
Autoimmune hepatitis  1  4/364 (1.10%)  1/362 (0.28%) 
Bile duct obstruction  1  0/364 (0.00%)  1/362 (0.28%) 
Biliary dilatation  1  0/364 (0.00%)  1/362 (0.28%) 
Cholangitis  1  0/364 (0.00%)  1/362 (0.28%) 
Drug-induced liver injury  1  1/364 (0.27%)  0/362 (0.00%) 
Hepatic failure  1  1/364 (0.27%)  0/362 (0.00%) 
Hepatitis  1  6/364 (1.65%)  2/362 (0.55%) 
Hepatitis acute  1  1/364 (0.27%)  0/362 (0.00%) 
Hepatocellular injury  1  5/364 (1.37%)  0/362 (0.00%) 
Hepatorenal syndrome  1  0/364 (0.00%)  1/362 (0.28%) 
Hepatotoxicity  1  2/364 (0.55%)  1/362 (0.28%) 
Hyperbilirubinaemia  1  0/364 (0.00%)  1/362 (0.28%) 
Jaundice  1  0/364 (0.00%)  1/362 (0.28%) 
Immune system disorders     
Hypersensitivity  1  2/364 (0.55%)  0/362 (0.00%) 
Infections and infestations     
Abdominal infection  1  0/364 (0.00%)  1/362 (0.28%) 
Bartholinitis  1  1/364 (0.27%)  0/362 (0.00%) 
Bronchitis  1  0/364 (0.00%)  1/362 (0.28%) 
Cellulitis  1  1/364 (0.27%)  0/362 (0.00%) 
Clostridium difficile colitis  1  0/364 (0.00%)  1/362 (0.28%) 
Cystitis  1  0/364 (0.00%)  1/362 (0.28%) 
Cytomegalovirus colitis  1  1/364 (0.27%)  1/362 (0.28%) 
Encephalitis  1  1/364 (0.27%)  0/362 (0.00%) 
Erysipelas  1  2/364 (0.55%)  2/362 (0.55%) 
Gastroenteritis viral  1  1/364 (0.27%)  0/362 (0.00%) 
Gastrointestinal infection  1  1/364 (0.27%)  0/362 (0.00%) 
Hepatitis viral  1  0/364 (0.00%)  1/362 (0.28%) 
Herpes zoster  1  0/364 (0.00%)  1/362 (0.28%) 
Infection  1  3/364 (0.82%)  0/362 (0.00%) 
Liver abscess  1  1/364 (0.27%)  0/362 (0.00%) 
Localised infection  1  0/364 (0.00%)  1/362 (0.28%) 
Lower respiratory tract infection  1  1/364 (0.27%)  1/362 (0.28%) 
Lung infection  1  2/364 (0.55%)  0/362 (0.00%) 
Lymph node abscess  1  0/364 (0.00%)  1/362 (0.28%) 
Necrotising fasciitis  1  0/364 (0.00%)  1/362 (0.28%) 
Peritonitis  1  0/364 (0.00%)  1/362 (0.28%) 
Pleural infection  1  1/364 (0.27%)  0/362 (0.00%) 
Pneumonia  1  5/364 (1.37%)  4/362 (1.10%) 
Pyelonephritis  1  1/364 (0.27%)  0/362 (0.00%) 
Sepsis  1  0/364 (0.00%)  2/362 (0.55%) 
Septic shock  1  2/364 (0.55%)  2/362 (0.55%) 
Staphylococcal infection  1  1/364 (0.27%)  0/362 (0.00%) 
Upper respiratory tract infection  1  0/364 (0.00%)  1/362 (0.28%) 
Urinary tract infection  1  0/364 (0.00%)  2/362 (0.55%) 
Viral infection  1  1/364 (0.27%)  0/362 (0.00%) 
Injury, poisoning and procedural complications     
Clavicle fracture  1  1/364 (0.27%)  0/362 (0.00%) 
Fibula fracture  1  0/364 (0.00%)  1/362 (0.28%) 
Hip fracture  1  1/364 (0.27%)  0/362 (0.00%) 
Infusion related reaction  1  1/364 (0.27%)  1/362 (0.28%) 
Post procedural haemorrhage  1  1/364 (0.27%)  0/362 (0.00%) 
Radiation dysphagia  1  0/364 (0.00%)  1/362 (0.28%) 
Wound haemorrhage  1  1/364 (0.27%)  0/362 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  6/364 (1.65%)  0/362 (0.00%) 
Aspartate aminotransferase increased  1  3/364 (0.82%)  0/362 (0.00%) 
Blood bilirubin increased  1  1/364 (0.27%)  0/362 (0.00%) 
Blood creatinine increased  1  1/364 (0.27%)  0/362 (0.00%) 
Blood glucose increased  1  1/364 (0.27%)  1/362 (0.28%) 
Blood potassium increased  1  1/364 (0.27%)  0/362 (0.00%) 
Gamma-glutamyltransferase increased  1  1/364 (0.27%)  0/362 (0.00%) 
Hepatic enzyme increased  1  1/364 (0.27%)  0/362 (0.00%) 
Liver function test increased  1  2/364 (0.55%)  0/362 (0.00%) 
Transaminases increased  1  3/364 (0.82%)  1/362 (0.28%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/364 (0.82%)  0/362 (0.00%) 
Dehydration  1  3/364 (0.82%)  2/362 (0.55%) 
Diabetic metabolic decompensation  1  1/364 (0.27%)  0/362 (0.00%) 
Hypercalcaemia  1  1/364 (0.27%)  1/362 (0.28%) 
Hyperglycaemia  1  1/364 (0.27%)  0/362 (0.00%) 
Hypokalaemia  1  1/364 (0.27%)  0/362 (0.00%) 
Hyponatraemia  1  3/364 (0.82%)  1/362 (0.28%) 
Ketoacidosis  1  1/364 (0.27%)  0/362 (0.00%) 
Tumour lysis syndrome  1  0/364 (0.00%)  1/362 (0.28%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/364 (0.00%)  1/362 (0.28%) 
Back pain  1  2/364 (0.55%)  1/362 (0.28%) 
Bone pain  1  2/364 (0.55%)  1/362 (0.28%) 
Flank pain  1  1/364 (0.27%)  0/362 (0.00%) 
Groin pain  1  2/364 (0.55%)  0/362 (0.00%) 
Muscular weakness  1  2/364 (0.55%)  2/362 (0.55%) 
Myalgia  1  1/364 (0.27%)  0/362 (0.00%) 
Pain in extremity  1  2/364 (0.55%)  0/362 (0.00%) 
Pathological fracture  1  1/364 (0.27%)  0/362 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/364 (0.27%)  0/362 (0.00%) 
Colon cancer  1  0/364 (0.00%)  1/362 (0.28%) 
Endometrial cancer  1  0/364 (0.00%)  1/362 (0.28%) 
Intracranial tumour haemorrhage  1  0/364 (0.00%)  2/362 (0.55%) 
Malignant melanoma in situ  1  1/364 (0.27%)  0/362 (0.00%) 
Malignant neoplasm progression  1  54/364 (14.84%)  60/362 (16.57%) 
Metastases to central nervous system  1  1/364 (0.27%)  4/362 (1.10%) 
Metastases to eye  1  1/364 (0.27%)  0/362 (0.00%) 
Metastases to meninges  1  1/364 (0.27%)  0/362 (0.00%) 
Metastases to muscle  1  0/364 (0.00%)  1/362 (0.28%) 
Metastases to skin  1  0/364 (0.00%)  1/362 (0.28%) 
Metastasis  1  0/364 (0.00%)  1/362 (0.28%) 
Neoplasm progression  1  0/364 (0.00%)  3/362 (0.83%) 
Neoplasm swelling  1  1/364 (0.27%)  0/362 (0.00%) 
Tumour associated fever  1  1/364 (0.27%)  0/362 (0.00%) 
Tumour haemorrhage  1  0/364 (0.00%)  3/362 (0.83%) 
Nervous system disorders     
Brain oedema  1  1/364 (0.27%)  0/362 (0.00%) 
Central nervous system haemorrhage  1  2/364 (0.55%)  0/362 (0.00%) 
Cerebellar haemorrhage  1  1/364 (0.27%)  1/362 (0.28%) 
Cerebral haematoma  1  1/364 (0.27%)  1/362 (0.28%) 
Cerebral haemorrhage  1  1/364 (0.27%)  1/362 (0.28%) 
Cerebrovascular accident  1  0/364 (0.00%)  1/362 (0.28%) 
Coma  1  0/364 (0.00%)  1/362 (0.28%) 
Epilepsy  1  1/364 (0.27%)  0/362 (0.00%) 
Facial nerve disorder  1  0/364 (0.00%)  1/362 (0.28%) 
Facial paralysis  1  1/364 (0.27%)  0/362 (0.00%) 
Facial paresis  1  1/364 (0.27%)  0/362 (0.00%) 
Guillain-barre syndrome  1  2/364 (0.55%)  0/362 (0.00%) 
Headache  1  5/364 (1.37%)  2/362 (0.55%) 
Hemiparesis  1  1/364 (0.27%)  0/362 (0.00%) 
Hemiplegia  1  0/364 (0.00%)  1/362 (0.28%) 
Intensive care unit acquired weakness  1  1/364 (0.27%)  0/362 (0.00%) 
Intracranial pressure increased  1  3/364 (0.82%)  0/362 (0.00%) 
Nervous system disorder  1  0/364 (0.00%)  1/362 (0.28%) 
Neuralgia  1  0/364 (0.00%)  1/362 (0.28%) 
Neurological decompensation  1  2/364 (0.55%)  0/362 (0.00%) 
Paralysis recurrent laryngeal nerve  1  0/364 (0.00%)  1/362 (0.28%) 
Partial seizures  1  0/364 (0.00%)  1/362 (0.28%) 
Peripheral motor neuropathy  1  1/364 (0.27%)  2/362 (0.55%) 
Sciatica  1  1/364 (0.27%)  1/362 (0.28%) 
Seizure  1  1/364 (0.27%)  2/362 (0.55%) 
Spinal cord compression  1  2/364 (0.55%)  2/362 (0.55%) 
Syncope  1  3/364 (0.82%)  1/362 (0.28%) 
Vasogenic cerebral oedema  1  0/364 (0.00%)  2/362 (0.55%) 
Psychiatric disorders     
Agitation  1  1/364 (0.27%)  0/362 (0.00%) 
Bipolar disorder  1  1/364 (0.27%)  0/362 (0.00%) 
Completed suicide  1  0/364 (0.00%)  1/362 (0.28%) 
Confusional state  1  2/364 (0.55%)  3/362 (0.83%) 
Depressed mood  1  2/364 (0.55%)  0/362 (0.00%) 
Mental status changes  1  0/364 (0.00%)  2/362 (0.55%) 
Renal and urinary disorders     
Acute kidney injury  1  1/364 (0.27%)  3/362 (0.83%) 
Nephritis  1  1/364 (0.27%)  0/362 (0.00%) 
Renal failure  1  3/364 (0.82%)  2/362 (0.55%) 
Tubulointerstitial nephritis  1  1/364 (0.27%)  0/362 (0.00%) 
Reproductive system and breast disorders     
Prostatitis  1  0/364 (0.00%)  1/362 (0.28%) 
Vaginal haemorrhage  1  0/364 (0.00%)  1/362 (0.28%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  0/364 (0.00%)  1/362 (0.28%) 
Acute respiratory failure  1  2/364 (0.55%)  0/362 (0.00%) 
Atelectasis  1  1/364 (0.27%)  0/362 (0.00%) 
Dyspnoea  1  6/364 (1.65%)  6/362 (1.66%) 
Epistaxis  1  1/364 (0.27%)  0/362 (0.00%) 
Haemoptysis  1  0/364 (0.00%)  1/362 (0.28%) 
Hydrothorax  1  0/364 (0.00%)  1/362 (0.28%) 
Pleural effusion  1  5/364 (1.37%)  4/362 (1.10%) 
Pneumonia aspiration  1  1/364 (0.27%)  0/362 (0.00%) 
Pneumonitis  1  4/364 (1.10%)  0/362 (0.00%) 
Pulmonary embolism  1  9/364 (2.47%)  4/362 (1.10%) 
Pulmonary microemboli  1  0/364 (0.00%)  1/362 (0.28%) 
Respiratory distress  1  1/364 (0.27%)  0/362 (0.00%) 
Respiratory failure  1  0/364 (0.00%)  1/362 (0.28%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic  1  1/364 (0.27%)  0/362 (0.00%) 
Haemorrhage subcutaneous  1  1/364 (0.27%)  0/362 (0.00%) 
Rash  1  1/364 (0.27%)  0/362 (0.00%) 
Rash pruritic  1  0/364 (0.00%)  1/362 (0.28%) 
Toxic skin eruption  1  1/364 (0.27%)  0/362 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/364 (0.27%)  2/362 (0.55%) 
Embolism  1  1/364 (0.27%)  0/362 (0.00%) 
Hypotension  1  1/364 (0.27%)  1/362 (0.28%) 
Thrombosis  1  1/364 (0.27%)  1/362 (0.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
10 MG/KG IPILIMUMAB 3 MG/KG IPILIMUMAB
Affected / at Risk (%) Affected / at Risk (%)
Total   319/364 (87.64%)   302/362 (83.43%) 
Blood and lymphatic system disorders     
Anaemia  1  24/364 (6.59%)  17/362 (4.70%) 
Gastrointestinal disorders     
Abdominal pain  1  33/364 (9.07%)  34/362 (9.39%) 
Constipation  1  38/364 (10.44%)  40/362 (11.05%) 
Diarrhoea  1  140/364 (38.46%)  105/362 (29.01%) 
Nausea  1  59/364 (16.21%)  74/362 (20.44%) 
Vomiting  1  43/364 (11.81%)  34/362 (9.39%) 
General disorders     
Asthenia  1  68/364 (18.68%)  60/362 (16.57%) 
Fatigue  1  86/364 (23.63%)  95/362 (26.24%) 
Oedema peripheral  1  25/364 (6.87%)  22/362 (6.08%) 
Pyrexia  1  59/364 (16.21%)  43/362 (11.88%) 
Investigations     
Alanine aminotransferase increased  1  27/364 (7.42%)  12/362 (3.31%) 
Aspartate aminotransferase increased  1  27/364 (7.42%)  8/362 (2.21%) 
Weight decreased  1  29/364 (7.97%)  25/362 (6.91%) 
Metabolism and nutrition disorders     
Decreased appetite  1  52/364 (14.29%)  51/362 (14.09%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  19/364 (5.22%)  26/362 (7.18%) 
Back pain  1  21/364 (5.77%)  20/362 (5.52%) 
Pain in extremity  1  26/364 (7.14%)  21/362 (5.80%) 
Nervous system disorders     
Dizziness  1  16/364 (4.40%)  22/362 (6.08%) 
Headache  1  56/364 (15.38%)  66/362 (18.23%) 
Psychiatric disorders     
Insomnia  1  19/364 (5.22%)  17/362 (4.70%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  33/364 (9.07%)  32/362 (8.84%) 
Dyspnoea  1  27/364 (7.42%)  26/362 (7.18%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  98/364 (26.92%)  103/362 (28.45%) 
Rash  1  106/364 (29.12%)  64/362 (17.68%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01515189     History of Changes
Other Study ID Numbers: CA184-169
2011-004029-28 ( EudraCT Number )
First Submitted: January 18, 2012
First Posted: January 24, 2012
Results First Submitted: February 3, 2017
Results First Posted: March 24, 2017
Last Update Posted: July 31, 2019