Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)
- Conditions
- Acute Myeloid Leukemia, in RelapseAcute Myeloid Leukemia Refractory
- Interventions
- Registration Number
- NCT05546580
- Lead Sponsor
- Oryzon Genomics S.A.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Diagnosis of primary AML or AML with myelodysplasia-related changes (AML-MRC)
- Patient is in first or second relapse or has refractory disease. Patients must have had histologic verification of AML at the original diagnosis.
- Patient must be positive for the following FLT3 mutations in bone marrow or PB: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) D835 or I836 or FLT3-ITD and specified FLT3-TKD.
- ECOG performance status 0-2
- Life expectancy of at least 3 months in the opinion of the investigator.
- Normal hepatic and renal function.
- Patient is able to swallow oral medications.
- Female patients are postmenopausal, documented as surgically sterile, use two methods of contraception or practice true abstinence and have a negative urine pregnancy test at screening.
- Male patients even if surgically sterilized agree to practice true abstinence or use highly effective barrier contraception.
Main
- Diagnosis of acute promyelocytic leukemia.
- Known BCR-ABL-positive leukemia.
- AML secondary to prior chemotherapy for other neoplasms (except for MDS).
- AML that has relapsed after or is refractory to more than 2 lines of therapy.
- Clinically active central nervous system leukemia or prior history of NCI CTCAE Grade ≥ 3 drug-related CNS toxicity.
- Major surgery or radiation therapy within 4 weeks prior to the first study dose.
- Prior treatment with iadademstat is not allowed. Treatment with any other agents with KDM1A/LSD1 inhibitory activity is only allowed if treatment finalized at least 3 weeks prior to first dose on study. Previous treatment with FLT3 inhibitors is allowed in the following cases: midostaurin and sorafenib are allowed when used in first-line therapy regimen as part of induction, consolidation and/or maintenance: quizartinib and gilteritinib are allowed when used in first-line therapy regimen, as part of induction, consolidation and/or maintenance, ONLY if patients were not refractory to the drugs or if responding, relapse did not occur while on these drugs.
- Patients not eligible to receive gilteritinib per label.
- Prior treatment with 3 or more lines of AML therapy.
- Treatment with any investigational products within 3 weeks prior to first dose of study treatment.
- Uncontrolled hypertension or poorly controlled diabetes.
- Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
- Pregnant or lactating women.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Active arm Gilteritinib Oral Tablet iadademstat and gilteritinib Active arm Iadademstat iadademstat and gilteritinib
- Primary Outcome Measures
Name Time Method Adverse Events (AE) Up to 18 months Number of participants with Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) Up to 18 months 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.
Recommend Phase 2 dose (RP2D) Up to 18 months Determine the recommended Phase 2 dose (RP2D) of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R
Laboratory value abnormalities and/or adverse events (AE) Up to 18 months 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.
Vital sign abnormalities and/or adverse events (AEs) Up to 18 months 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.
iadademstat tmax Up to 26 days Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.
Iadademstat Cmax Up to 26 days Measurement of the highest concentration of iadademstat in the blood after a dose is given.
iadademstat Cmin Up to 26 days Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.
iadademstat AUC Up to 26 days Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.
iadademstat Target Engagement (TE) Up to 26 days Percent of drug covalently bound to LSD1 molecule
OR rate Up to 18 months Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to 24 months Time from start of treatment to the time of death from any cause.
Overall response rate Up to 6 months Percentage of patients with complete remission (CR), CR with incomplete blood count recovery (CRi), or PR.
Event-Free-Survival (EFS) Up to 18 months 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.
Transplantation Rate Time Frame Up to 18 months Percentage of patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) during the study period.
Time to Response (TTR) Up to 6 months Time from the date of initial dosing at RP2D/expansion dose to first documentation of either a type of CR or Partial Response (PR).
Duration of Remission (DoR) Up to 18 months Time from the date of first documentation of any type of remission to the date of first documentation of progression of remission for remitters
Transfusion independence rate Up to 18 months 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).
Trial Locations
- Locations (13)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
The John Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital (MGH)
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute, LLC
🇺🇸Nashville, Tennessee, United States
Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital
🇺🇸New York, New York, United States
Rutgers, The State University
🇺🇸Piscataway, New Jersey, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
The University of Arizona Cancer Center - North Campus
🇺🇸Tucson, Arizona, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Froedtert Hospital & The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States