Iadademstat is being studied as a treatment for subjects with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) with FMS-like tyrosine kinase mutation (FLT3 mut+). During the trial, iadademstat will be given in combination with gilteritinib, a drug that is already approved to treat patients with FLT3-mutated R/R AML.
This is an escalation/expansion, open label, single arm, study to investigate the safety and the RP2D of the combination of iadademstat with gilteritinib in FLT3-mutated R/R AML. This study consists of 2 parts. A dose finding part to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and emerging activity of iadademstat and gilteritinib combination, and to determine the pharmacologically-active dose (i.e., the minimum safe and biologically active dose) of iadademstat in combination with gilteritinib, and an expansion part at the specific dose/s selected to evaluate the activity of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
iadademstat oral solution
120 mg Gilteritinib
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
RECRUITINGThe University of Arizona Cancer Center - North Campus
Tucson, Arizona, United States
Adverse Events (AE)
Number of participants with Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Time frame: Up to 18 months
Laboratory value abnormalities and/or adverse events (AE)
Number of participants with laboratory value abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Time frame: Up to 18 months
Vital sign abnormalities and/or adverse events (AEs)
Number of participants with vital signs abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Time frame: Up to 18 months
Routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Number of participants with Routine 12-lead electrocardiogram (ECG )abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Time frame: Up to 18 months
Recommend Phase 2 dose (RP2D)
Determine the recommended Phase 2 dose (RP2D) of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R
Time frame: Up to 18 months
iadademstat tmax
Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.
Time frame: Up to 26 days
Iadademstat Cmax
Measurement of the highest concentration of iadademstat in the blood after a dose is given.
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Sylvester Comprehensive Cancer Center
Miami, Florida, United States
RECRUITINGMiami Cancer Institute
Miami, Florida, United States
RECRUITINGThe John Hopkins University School of Medicine
Baltimore, Maryland, United States
RECRUITINGMassachusetts General Hospital (MGH)
Boston, Massachusetts, United States
RECRUITINGRutgers, The State University
Piscataway, New Jersey, United States
RECRUITINGIcahn School of Medicine at Mount Sinai and Mount Sinai Hospital
New York, New York, United States
RECRUITINGDuke University Medical Center
Durham, North Carolina, United States
RECRUITINGOregon Health & Science University
Portland, Oregon, United States
RECRUITING...and 3 more locations
Time frame: Up to 26 days
iadademstat Cmin
Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.
Time frame: Up to 26 days
iadademstat AUC
Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.
Time frame: Up to 26 days
iadademstat Target Engagement (TE)
Percent of drug covalently bound to LSD1 molecule
Time frame: Up to 26 days
OR rate
Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).
Time frame: Up to 18 months
Overall Survival (OS)
Time from start of treatment to the time of death from any cause.
Time frame: Up to 24 months
Event-Free-Survival (EFS)
Time from start of treatment to the date of failure to achieve CR or CRi, relapse from CR/CRi, or death from any cause, whichever occurs first.
Time frame: Up to 18 months
Overall response rate
Percentage of patients with complete remission (CR), CR with incomplete blood count recovery (CRi), or PR.
Time frame: Up to 6 months
Time to Response (TTR)
Time from the date of initial dosing at RP2D/expansion dose to first documentation of either a type of CR or Partial Response (PR).
Time frame: Up to 6 months
Duration of Remission (DoR)
Time from the date of first documentation of any type of remission to the date of first documentation of progression of remission for remitters
Time frame: Up to 18 months
Transfusion independence rate
A patient is defined as red blood cell (RBC) and/or platelet-transfusion independent if he/she receives no RBC and/or platelet transfusions for a period of at least 8 weeks. Rate of transfusion independence is the percentage of patients who become RBC and/or platelet transfusion independent (from the number of patients transfusion dependent at baseline).
Time frame: Up to 18 months
Transplantation Rate Time Frame
Percentage of patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) during the study period.
Time frame: Up to 18 months