A Study of CSL362 in Patients With CD123+ Acute Myeloid Leukemia Currently in Remission
This is a first in human, prospective, multicenter, nonrandomized, open-label, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of repeat doses of CSL362.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of CSL362 (Anti-IL3Rα / Anti-CD123 Monoclonal Antibody) in Patients With CD123+ Acute Myeloid Leukemia in Complete Remission or Complete Remission With Incomplete Platelet Recovery at High Risk for Early Relapse|
- Frequency and Severity of Adverse Events (AEs) [ Time Frame: From the first treatment (Day 1) up to approximately Day 106 ] [ Designated as safety issue: Yes ]Number of subjects reporting any AEs and the severity of those AEs.
- Dose-limiting toxicity (DLT) evaluation [ Time Frame: From the first treatment (Day 1) up to approximately Day 106 ] [ Designated as safety issue: Yes ]
Number of participants with DLT.
Dose-limiting toxicity (DLT) is defined as:
- A non-hematological toxicity grade 3 or worse.
- A hematological toxicity grade 3 that does not recover to baseline within 14 days.
- A hematological toxicity grade 4 or worse according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
- Pharmacokinetic (PK) Parameters [ Time Frame: Before each infusion and: at 6 time points within a week after infusion 1, at 1 time point within a week after infusions 2 to 5, at 5 time points within a week after infusion 6, and once at the final visit, approximately 5 weeks after infusion 6 ] [ Designated as safety issue: No ]
PK Parameters comprise:
Area under the serum concentration time curve (AUC) from time point zero (before dosing):
- to the time point at which the analyte first returns to baseline (AUC0-last)
- to a meaningful time after infusion (AUC0-y)
- extrapolated to infinity (AUC0-∞).
- The maximum observed serum concentration (Cmax).
- First time to reach maximum concentration in serum (Tmax).
- Terminal serum half-life (t 1/2)
- Number of subjects developing antibodies against CSL362 [ Time Frame: From the first treatment (Day 1) up to approximately Day 106 ] [ Designated as safety issue: No ]
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
See Intervention Description
CSL362 is humanized monoclonal antibody that targets the alpha chain of the interleukin 3 receptor (IL3Rα; also known as CD123) and is optimised for enhanced activation of antibody-dependent cell-mediated cytotoxicity (ADCC) via natural killer cells.
CSL362 is a sterile solution for injection and will be administered by intravenous infusion to subjects in sequential, escalating dose level cohorts, at doses up to 12.0 mg/kg. CSL362 will be administered every 14 days for a total of 6 infusions per subject. The 6 infusions for each individual subject will contain the same dose of CSL362.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01632852
|United States, Illinois|
|Robert H. Lurie Comprehensive Cancer Center of Northwestern University Medical School|
|Chicago, Illinois, United States, 60611|
|United States, Maryland|
|Sidney Kimmel Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21287|
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Royal Melbourne Hospital|
|Parkville, Victoria, Australia, 3050|
|Study Director:||Dr. Mark DeWitte||CSL Limited|