Evaluation of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia (AML)
This Phase 1b study will determine the maximum tolerated dose of KX2-391 given as a once-daily dose, in elderly patients with acute myelogenous leukemia.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1b Rising Multiple-Dose Study to Evaluate Safety, Tolerability and Activity of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia Who Are Refractory to or Have Declined Standard Induction Therapy|
- To determine the maximum tolerated dose of KX2-391 when given once-daily to AML patients. [ Time Frame: 28 days ] [ Designated as safety issue: No ]The MTD will be used to determine the recommended Phase 2 dose that is associated with an approximately 33% DLT rate during the first 28 days of treatment in elderly patients with AML
- Evaluate pharmacokinetics, pharmacodynamics and activity of KX2-391. [ Time Frame: 28 days ] [ Designated as safety issue: No ]The pharmacokinetics and pharmacodynamics of KX2-391 will be evaluated in AML patients by measuring serum and bone marrow levels of drug and evaluating the disruption of microtubule networks in these samples to determine whether target inhibition has occurred at the doses tested. Hematological and bone marrow response will be assessed according to International Working Group (IWG)-AML criteria.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||October 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Subjects will be enrolled into a 28-day dose-escalation study. If no DLT's are observed during the first 28 days, subjects are eligible to continue treatment in the Extension Phase and can remain on treatment until toxicity occurs or until disease progression.
Oral dose solution, once-daily dosing for 28-days. Subjects may continue beyond the first 28-days until disease progression or unacceptable toxicity develops.
Other Name: KX01
KX2-391 has been evaluated in a Phase 1 dose escalation study in patients with solid tumors using twice-daily dosing. This study will employ the Storer's two-stage design to determine the maximum tolerated dose of KX2-391 mono-therapy,given as a once-daily oral dose,in elderly patients with acute myelogenous leukemia (AML) who are refractory to or have declined standard induction therapy. The safety, tolerability, pharmacokinetics and activity of KX2-391 will be evaluated.
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||James Thompson, MD||Roswell Park Cancer Institute|