Comparison of Ipilimumab Manufactured by 2 Different Processes in Participants With Advanced Melanoma

This study has been completed.
Sponsor:
Collaborator:
Medarex
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00920907
First received: June 9, 2009
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Advanced Melanoma
Biological: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Serum Concentration (Cmax) of Ipilimumab Manufactured by Process C Relative to the Cmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population [ Time Frame: Day 1 to Day 84 ] [ Designated as safety issue: No ]
    Single-dose Pharmacokinetic (PK) parameters of ipilimumab were derived from serum concentration versus time data. Cmax was measured from first dose to end of the induction period (4 doses) as micrograms per milliliter (μg/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

  • 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 [ Time Frame: Day 1 to Day 84 ] [ Designated as safety issue: No ]
    The single-dose pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. AUC(0-21d) was measured from first dose to end of the induction period as micrograms*hours per milliliter (μg*h/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).


Secondary Outcome Measures:
  • 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 [ Time Frame: Day 1 to Day 84 ] [ Designated as safety issue: No ]
    The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. Tmax was measured from first dose to end of the induction period (4 doses) in hours (h). Samples were obtained at 0 h (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

  • 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 [ Time Frame: Day 1 to Day 84 ] [ Designated as safety issue: No ]
    The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. T-HALF was measured from first dose to end of the induction period (4 doses) in day(s). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

  • Clearance (CLT) of Ipilimumab Manufactured by Process C Relative to the CLT of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population [ Time Frame: Day 1 to Day 84 ] [ Designated as safety issue: No ]
    The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. CLT was measured from first dose to end of the induction period (4 doses) in milliliters per hour (mL/h). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

  • 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 [ Time Frame: Day 1 to Day 84 ] [ Designated as safety issue: No ]
    The single-dose Pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. Vss was measured from first dose to end of the induction period (4 doses) in liter(s) (L). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox [version 2.6.1]).

  • Absolute Lymphocyte Count Assessed as Pharmacodynamic Marker Pre- and Post- Treatment [ Time Frame: Up to Week 48 on treatment ] [ Designated as safety issue: Yes ]
  • Safety Assessments Based on Adverse Event Reports, Vital Sign Measurements, Physical Examinations, Clinical Laboratory Tests, and Development of Human Anti-human Antibodies [ Time Frame: Up to Week 48 on treatment ] [ Designated as safety issue: Yes ]
  • Tumor Response Evaluations [ Time Frame: Up to Week 48 on treatment ] [ Designated as safety issue: Yes ]

Enrollment: 99
Study Start Date: August 2009
Study Completion Date: October 2012
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab (Process B)
Reference
Biological: Ipilimumab
Solution, Intravenous, 10 mg/kg, Every 3 weeks (up to 4 doses) in induction phase, every 12 weeks in maintenance phase, 48 weeks
Other Names:
  • BMS-734016
  • MDX010
Experimental: Ipilimumab (Process C)
Test
Biological: Ipilimumab
Solution, Intravenous, 10 mg/kg, Every 3 weeks (up to 4 doses) in induction phase, every 12 weeks in maintenance phase, 48 weeks
Other Names:
  • BMS-734016
  • MDX010

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00920907

Locations
United States, California
The Angeles Clinic & Research Inst.
Los Angeles, California, United States, 90025
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Florida
H Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612-9416
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 11065
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
St Luke'S Hospital And Health Network
Bethlehem, Pennsylvania, United States, 18015
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Sponsors and Collaborators
Bristol-Myers Squibb
Medarex
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00920907     History of Changes
Other Study ID Numbers: CA184-087
Study First Received: June 9, 2009
Results First Received: November 25, 2013
Last Updated: January 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 15, 2014