An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Multiple Dose Administrations of Anti-KIR (1-7F9) Human Monoclonal Antibody in Subjects With Multiple Myeloma|
- Maximum Tolerated Dose (MTD) of IPH2101 as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to IPH2101 Treatment [ Time Frame: From start of the treatment to end of study ] [ Designated as safety issue: Yes ]The maximum tolerated dose (MTD) is the highest dose level below the maximum administered dose (MAD) where none or 1 out of 6 subjects have a DLT.
- Maximum Plasma Concentration (Cmax) of IPH2101 After Cycle 1 Administration [ Time Frame: Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration ] [ Designated as safety issue: No ]Cmax was obtained from the plasma concentration versus time data after IV administration of IPH2101.
- Area Under the Plasma-concentration-time Curve [AUC (INF)] of IPH2101 After Cycle 1 Administration [ Time Frame: Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration ] [ Designated as safety issue: No ]AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Cycle 1.
- Number of Evaluable Patients With Stable Disease. "Evaluable" is Defined as 2 Consecutive M Protein Assessments [ Time Frame: From start of the treatment to end of study or disease progression ] [ Designated as safety issue: No ]Disease Response Assessment by Principal Investigator and Sponsor(Efficacy Population).Stable Disease was defined as not meeting criteria for complete response, very good partial response, partial response, or progressive disease
|Study Start Date:||May 2007|
|Study Completion Date:||January 2011|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
Drug: Anti-KIR (1-7F9)
The trial is an open-label, dose-escalation trial to determine the safety and tolerability of Anti-KIR (1-7F9) in subjects with relapsed or refractory multiple myeloma (RRMM). A 3+3 design will be employed for the first dosing cycle at each dose level. The 7 planned dose levels are 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg. The subjects will receive up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks. Safety, toxicity, PK (pharmacokinetic) and PD (pharmacodynamic) obtained in the first 4 weeks after dosing per group will be the basis for dose-escalation decisions. There will be follow-up visits every week the one month after the first administration and every two weeks following the second, third and fourth administrations. After the last administration there will be follow-up visits every month until KIR occupancy is no longer detected.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00552396
|United States, Indiana|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, New York|
|Mont Sinai Medical Center|
|New York City, New York, United States, 10029|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|Cancer Therapy Research Center at UTHSCSA|
|San Antonio, Texas, United States, 78229-4427|
|Principal Investigator:||Sherif Farag, MD, PhD||Indiana University|
|Principal Investigator:||Don Benson, Jr., MD, PhD||Division of Haematology/Oncology - Ohio State University|
|Principal Investigator:||Swaminathan Padmanabhan, MD||CTRC Institute for Drug Development - University of Texas at San Antonio|
|Principal Investigator:||Sundar Jagannath, MD||Mount Sinai Hospital, New York|