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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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00094653
First received: October 21, 2004
Last updated: June 29, 2011
Last verified: June 2011
Results First Received: April 22, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: Melanoma
Metastases
Interventions: Drug: MDX-010 (anti-CTLA4) monoclonal antibody
Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 1783 participants who enrolled and were screened for study participation, a total of 676 subjects were randomized.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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.

Participant Flow:   Overall Study
    Ipilimumab Plus gp100   Ipilimumab Monotherapy   gp100
STARTED   403   137   136 
Treated   381   131   131 
COMPLETED   82   31   10 
NOT COMPLETED   321   106   126 
Death                306                100                119 
Subject Withdrew Consent                10                2                3 
Not specified                2                2                2 
Lost to Follow-up                3                2                1 
Protocol Violation                0                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ipilimumab Plus gp100 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 Monotherapy 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 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 Total of all reporting groups

Baseline Measures
   Ipilimumab Plus gp100   Ipilimumab Monotherapy   gp100   Total 
Overall Participants Analyzed 
[Units: Participants]
 403   137   136   676 
Age 
[Units: Years]
Mean (Full Range)
 55.6 
 (24 to 84) 
 56.8 
 (19 to 88) 
 57.4 
 (23 to 90) 
 56.2 
 (19 to 90) 
Age, Customized 
[Units: Participants]
       
< 65 years   291   95   94   480 
>=65 years   112   42   42   196 
Gender 
[Units: Participants]
       
Female   156   56   63   275 
Male   247   81   73   401 
Race/Ethnicity, Customized 
[Units: Participants]
       
White   380   129   129   638 
Black   3   1   1   5 
Hispanic   18   7   5   30 
Other   2   0   1   3 
Duration of Melanoma [1] 
[Units: Years]
Mean (Full Range)
 5.09 
 (0.2 to 38.9) 
 4.34 
 (-0.0 to 35.9) 
 5.65 
 (0.3 to 31.2) 
 5.05 
 (-0.0 to 38.9) 
[1] Duration of melanoma is the number of years from date of initial diagnosis to the date of randomization. The randomization of 1 participant in the ipilumumab monotherapy cohort was prior to the initial diagnostic date. Data for 2 participants in the ipilimumab + gp100 cohort were missing.
Melanoma Stage [1] 
[Units: Participants]
       
M0   5   1   4   10 
M1a   37   14   11   62 
M1b   76   22   23   121 
M1c   285   100   98   483 
[1] The "M" in the TNM (tumor, node, metastasis) system refers to distant metastases—whether, and how far, the cancer has spread outside the original site. M0: There is no evidence that the cancer has spread beyond the original site. M1: The cancer has spread beyond the original site. M1a: The cancer has spread to other areas of skin, underneath the epidermis to the dermis (subcutaneous), or to lymph node(s). M1b: The cancer has spread to the lung(s) only. M1c: The cancer has spread to other organs and/or locations in the body with or without elevated LDH.
Prior Interleukin-2 Therapy 
[Units: Participants]
       
No   314   105   103   522 
Yes   89   32   33   154 
Lactate Dehydrogenase [1] 
[Units: Participants]
       
>upper limit of normal (ULN)   149   53   52   254 
<=ULN   252   84   81   417 
unknown   2   0   3   5 
[1] Upper limit of normal (ULN) was 250 U/L for most assessments (some variation caused by tests performed at local laboratories).


  Outcome Measures
  Show All Outcome Measures

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

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

3.  Secondary:   12-, 18-, and 24-Month Survival Rates   [ Time Frame: Month 12, Month 18, Month 24 ]

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

5.  Secondary:   Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24   [ Time Frame: Week 12, Week 24 ]

6.  Secondary:   Time to Progression (TTP)   [ 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]) ]

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

8.  Secondary:   Determination of Best Overall Response Rate (BORR)   [ Time Frame: Up to week 24 ]

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

10.  Secondary:   Duration of Response   [ 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]) ]

11.  Secondary:   Disease Control Rate (DCR)   [ Time Frame: Up to week 24 ]

12.  Secondary:   Delayed Response (Response Beyond Week 24)   [ 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]) ]

13.  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   [ Time Frame: Baseline (Day 1, Cycle1), Week 12 ]

14.  Secondary:   Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death   [ 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]). ]

15.  Secondary:   Percentage of Participants With Immune-Related Adverse Events (irAEs)   [ 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]). ]

16.  Secondary:   Percentage of Participants With Worst On-Study Hematological Abnormalities   [ 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]). ]

17.  Secondary:   Percentage of Participants With Worst On-Study Liver Abnormalities   [ 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]). ]

18.  Secondary:   Percentage of Participants With Worst On-Study Renal Abnormalities   [ 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]). ]

19.  Secondary:   Clinically Meaningful Changes in Vital Signs and Physical Examinations   [ 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 ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Ipilimumab Monotherapy 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 Plus gp100 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 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.

Other Adverse Events
    Ipilimumab Monotherapy   Ipilimumab Plus gp100   gp100
Total, other (not including serious) adverse events       
# participants affected / at risk   124/131 (94.66%)   362/380 (95.26%)   124/132 (93.94%) 
Blood and lymphatic system disorders       
ANAEMIA † 1       
# participants affected / at risk   14/131 (10.69%)   36/380 (9.47%)   22/132 (16.67%) 
Gastrointestinal disorders       
ABDOMINAL DISTENSION † 1       
# participants affected / at risk   0/131 (0.00%)   13/380 (3.42%)   9/132 (6.82%) 
ABDOMINAL PAIN † 1       
# participants affected / at risk   20/131 (15.27%)   64/380 (16.84%)   18/132 (13.64%) 
ABDOMINAL PAIN UPPER † 1       
# participants affected / at risk   7/131 (5.34%)   17/380 (4.47%)   11/132 (8.33%) 
CONSTIPATION † 1       
# participants affected / at risk   27/131 (20.61%)   79/380 (20.79%)   34/132 (25.76%) 
DIARRHOEA † 1       
# participants affected / at risk   41/131 (31.30%)   142/380 (37.37%)   26/132 (19.70%) 
DYSPEPSIA † 1       
# participants affected / at risk   2/131 (1.53%)   14/380 (3.68%)   10/132 (7.58%) 
FLATULENCE † 1       
# participants affected / at risk   3/131 (2.29%)   9/380 (2.37%)   8/132 (6.06%) 
NAUSEA † 1       
# participants affected / at risk   44/131 (33.59%)   127/380 (33.42%)   49/132 (37.12%) 
VOMITING † 1       
# participants affected / at risk   30/131 (22.90%)   71/380 (18.68%)   27/132 (20.45%) 
General disorders       
ADVERSE EVENT † 1       
# participants affected / at risk   4/131 (3.05%)   22/380 (5.79%)   5/132 (3.79%) 
ASTHENIA † 1       
# participants affected / at risk   6/131 (4.58%)   37/380 (9.74%)   17/132 (12.88%) 
CHILLS † 1       
# participants affected / at risk   9/131 (6.87%)   23/380 (6.05%)   7/132 (5.30%) 
FATIGUE † 1       
# participants affected / at risk   55/131 (41.98%)   137/380 (36.05%)   41/132 (31.06%) 
INFLUENZA LIKE ILLNESS † 1       
# participants affected / at risk   7/131 (5.34%)   20/380 (5.26%)   3/132 (2.27%) 
INJECTION SITE ERYTHEMA † 1       
# participants affected / at risk   1/131 (0.76%)   26/380 (6.84%)   5/132 (3.79%) 
INJECTION SITE INDURATION † 1       
# participants affected / at risk   0/131 (0.00%)   25/380 (6.58%)   4/132 (3.03%) 
INJECTION SITE PAIN † 1       
# participants affected / at risk   2/131 (1.53%)   25/380 (6.58%)   13/132 (9.85%) 
INJECTION SITE REACTION † 1       
# participants affected / at risk   2/131 (1.53%)   109/380 (28.68%)   26/132 (19.70%) 
OEDEMA PERIPHERAL † 1       
# participants affected / at risk   12/131 (9.16%)   47/380 (12.37%)   22/132 (16.67%) 
PAIN † 1       
# participants affected / at risk   6/131 (4.58%)   23/380 (6.05%)   15/132 (11.36%) 
PYREXIA † 1       
# participants affected / at risk   15/131 (11.45%)   74/380 (19.47%)   23/132 (17.42%) 
Infections and infestations       
URINARY TRACT INFECTION † 1       
# participants affected / at risk   8/131 (6.11%)   8/380 (2.11%)   4/132 (3.03%) 
Investigations       
WEIGHT DECREASED † 1       
# participants affected / at risk   8/131 (6.11%)   33/380 (8.68%)   12/132 (9.09%) 
Metabolism and nutrition disorders       
DECREASED APPETITE † 1       
# participants affected / at risk   33/131 (25.19%)   85/380 (22.37%)   29/132 (21.97%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA † 1       
# participants affected / at risk   12/131 (9.16%)   30/380 (7.89%)   14/132 (10.61%) 
BACK PAIN † 1       
# participants affected / at risk   9/131 (6.87%)   32/380 (8.42%)   16/132 (12.12%) 
MUSCULOSKELETAL CHEST PAIN † 1       
# participants affected / at risk   7/131 (5.34%)   7/380 (1.84%)   2/132 (1.52%) 
MUSCULOSKELETAL PAIN † 1       
# participants affected / at risk   5/131 (3.82%)   30/380 (7.89%)   10/132 (7.58%) 
MYALGIA † 1       
# participants affected / at risk   8/131 (6.11%)   28/380 (7.37%)   4/132 (3.03%) 
PAIN IN EXTREMITY † 1       
# participants affected / at risk   9/131 (6.87%)   51/380 (13.42%)   19/132 (14.39%) 
Nervous system disorders       
DIZZINESS † 1       
# participants affected / at risk   5/131 (3.82%)   27/380 (7.11%)   13/132 (9.85%) 
HEADACHE † 1       
# participants affected / at risk   19/131 (14.50%)   64/380 (16.84%)   18/132 (13.64%) 
Psychiatric disorders       
ANXIETY † 1       
# participants affected / at risk   5/131 (3.82%)   31/380 (8.16%)   9/132 (6.82%) 
INSOMNIA † 1       
# participants affected / at risk   16/131 (12.21%)   33/380 (8.68%)   15/132 (11.36%) 
Respiratory, thoracic and mediastinal disorders       
COUGH † 1       
# participants affected / at risk   21/131 (16.03%)   55/380 (14.47%)   17/132 (12.88%) 
DYSPNOEA † 1       
# participants affected / at risk   16/131 (12.21%)   45/380 (11.84%)   20/132 (15.15%) 
Skin and subcutaneous tissue disorders       
ERYTHEMA † 1       
# participants affected / at risk   10/131 (7.63%)   26/380 (6.84%)   7/132 (5.30%) 
HYPERHIDROSIS † 1       
# participants affected / at risk   6/131 (4.58%)   14/380 (3.68%)   12/132 (9.09%) 
PRURITUS † 1       
# participants affected / at risk   39/131 (29.77%)   79/380 (20.79%)   14/132 (10.61%) 
RASH † 1       
# participants affected / at risk   29/131 (22.14%)   78/380 (20.53%)   9/132 (6.82%) 
Vascular disorders       
HOT FLUSH † 1       
# participants affected / at risk   6/131 (4.58%)   8/380 (2.11%)   8/132 (6.06%) 
HYPOTENSION † 1       
# participants affected / at risk   8/131 (6.11%)   12/380 (3.16%)   4/132 (3.03%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 12.1



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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