Clinical trial NCT00920907: Comparison of Ipilimumab Manufactured by 2 Different Processes in Participants With Advanced Melanoma
Official title: A Randomized, Parallel, Open-Label Study to Compare the Pharmacokinetics of Ipilimumab (BMS-734016) Process C to Process B in Subjects With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Medarex
First posted: 2009-06-15
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to compare pharmacokinetics of ipilimumab manufactured by two different processes


Eligibility criteria: Inclusion Criteria:

* Histologic diagnosis of malignant melanoma
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Measurable/evaluable disease per modified World Health Organization (mWHO) criteria

Exclusion Criteria:

* Active Brain Metastasis
* Primary ocular or mucosal melanoma
* Prior Autoimmune disease
* Inadequate hematologic, hepatic or renal function
* Use of immunosuppressants
* Prior treatment with a CD137 agonist or cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Ipilimumab Manufactured by Process C Relative to the Cmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
timeFrame: Day 1 to Day 84
measure: Area Under the Serum Concentration-time Curve (AUC) From Time Zero to Day 21, AUC(0-21d), of Ipilimumab Manufactured by Process C Relative to the AUC(0-21d) of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
timeFrame: Day 1 to Day 84
Secondary outcomes:
measure: Time of Maximum Observed Serum Concentration (Tmax) of Ipilimumab Manufactured by Process C Relative to the Tmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
timeFrame: Day 1 to Day 84
measure: Terminal Elimination Half Life (T-HALF) of Ipilimumab Manufactured by Process C Relative to the T-HALF of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
timeFrame: Day 1 to Day 84
measure: Clearance (CLT) of Ipilimumab Manufactured by Process C Relative to the CLT of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
timeFrame: Day 1 to Day 84
measure: Volume of Distribution at Steady State (Vss) of Ipilimumab Manufactured by Process C Relative to the Vss of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
timeFrame: Day 1 to Day 84
measure: Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants
timeFrame: Day 1 to last patient, last visit, approximately 3 years
measure: Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants
timeFrame: Day 1 to last patient, last visit, approximately 3 years
measure: Median Overall Survival Following First Ipilimumab Dose - All Treated Participants
timeFrame: Week 1 (first dose) to last patient, last visit, approximately 3 years
measure: Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period
timeFrame: Day 0 (prior to first dose) to Day 84
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation
timeFrame: Day 1 to last patient, last visit, approximately 3 years
measure: Number of Participants Who Developed Antibodies and Neutralizing Antibodies
timeFrame: Prior to start of drug Week 1 to Week 24 on treatment or end of treatment
measure: Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff
timeFrame: Screening to data cut off for July 2010, approximately 36 Weeks
measure: Mean Change From Baseline in Sitting Pulse Rate - All Treated Participants up to Data Cutoff
timeFrame: Screening to data cut off for July 2010, approximately 36 Weeks
measure: Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants
timeFrame: Screening to data cut off for July 2010, approximately 36 Weeks
measure: Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants
timeFrame: Screening to data cut off for July 2010, approximately 36 Weeks
measure: Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants
timeFrame: Screening to data cut off for July 2010, approximately 36 Weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Inst.
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Bethlehem
country: United States
facility: St Luke'S Hospital And Health Network
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kitano S, Postow MA, Ziegler CG, Kuk D, Panageas KS, Cortez C, Rasalan T, Adamow M, Yuan J, Wong P, Altan-Bonnet G, Wolchok JD, Lesokhin AM. Computational algorithm-driven evaluation of monocytic myeloid-derived suppressor cell frequency for prediction of clinical outcomes. Cancer Immunol Res. 2014 Aug;2(8):812-21. doi: 10.1158/2326-6066.CIR-14-0013. Epub 2014 May 20.
citation: Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014 Apr 2;6(230):230ra45. doi: 10.1126/scitranslmed.3008002.