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

NCT00920907 | Completed Phase 1 Results

• 1 other identifier: CA184-087
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Advanced Melanoma

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Serum Concentration (Cmax) of Ipilimumab Manufactured by Process C Relative to the Cmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population

  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 \[version 2.6.1\]).

  Day 1 to Day 84

• 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

  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 \[version 2.6.1\]).

  Day 1 to Day 84

Secondary Outcomes (15)

• 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

  Day 1 to Day 84

• 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

  Day 1 to Day 84

• Clearance (CLT) of Ipilimumab Manufactured by Process C Relative to the CLT of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population

  Day 1 to Day 84

• 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

  Day 1 to Day 84

• Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants

  Day 1 to last patient, last visit, approximately 3 years

Study Arms (2)

Ipilimumab (Process B)

EXPERIMENTAL

Reference

Biological: Ipilimumab

Ipilimumab (Process C)

EXPERIMENTAL

Test

Biological: Ipilimumab

Interventions

Ipilimumab BIOLOGICAL

Solution, Intravenous, 10 mg/kg, Every 3 weeks (up to 4 doses) in induction phase, every 12 weeks in maintenance phase, 48 weeks

Also known as: BMS-734016, MDX010

Ipilimumab (Process B); Ipilimumab (Process C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Medarex: collaborator

Study Sites (7)

The Angeles Clinic & Research Inst.

Los Angeles, California, 90025, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

H Lee Moffitt Cancer Center

Tampa, Florida, 33612-9416, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 11065, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

St Luke'S Hospital And Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

Related Publications (2)

• 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.

  PMID: 24844912 DERIVED

• 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.

  PMID: 24695685 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Interventions

Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2009
• First Posted: June 15, 2009
• Study Start: August 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: October 1, 2012
• Last Updated: June 20, 2014
• Results First Posted: March 6, 2014

Record last verified: 2014-05

Locations

US (7)