Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)

Acute Myeloid Leukemia, in Relapse Clinical Trial

— FRIDA  

Official title:

An Escalation/Expansion, Open Label, Multicenter Study of Iadademstat and Gilteritinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+): The FRIDA Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05546580
• Other study ID #: CL04-ORY-1001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 14, 2022
• Est. completion date: July 30, 2025

Study information

• Verified date: June 2023
• Source: Oryzon Genomics S.A.
• Contact: Ana Limón, PhD
• Phone: +34 935151313
• Email: FRIDA_queries[@]oryzon.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 30, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

• 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 Exclusion Criteria:

• 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 or FLT3 inhibitors (except sorafenib or midostaurin used in first line as part of induction).
• 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Refractory
• Acute Myeloid Leukemia, in Relapse
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Iadademstat
iadademstat oral solution
• Gilteritinib Oral Tablet
120 mg Gilteritinib

Locations

Country	Name	City	State
United States	The John Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Miami Cancer Institute	Miami	Florida
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Froedtert Hospital & The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
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	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	The University of Arizona Cancer Center - North Campus	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Oryzon Genomics S.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 18 months
Primary	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.	Up to 18 months
Primary	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.	Up to 18 months
Primary	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.	Up to 18 months
Primary	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	Up to 18 months
Primary	iadademstat tmax	Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.	Up to 26 days
Primary	Iadademstat Cmax	Measurement of the highest concentration of iadademstat in the blood after a dose is given.	Up to 26 days
Primary	iadademstat Cmin	Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.	Up to 26 days
Primary	iadademstat AUC	Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.	Up to 26 days
Primary	iadademstat Target Engagement (TE)	Percent of drug covalently bound to LSD1 molecule	Up to 26 days
Primary	OR rate	Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).	Up to 18 months
Secondary	Overall Survival (OS)	Time from start of treatment to the time of death from any cause.	Up to 24 months
Secondary	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.	Up to 18 months
Secondary	Overall response rate	Percentage of patients with complete remission (CR), CR with incomplete blood count recovery (CRi), or PR.	Up to 6 months
Secondary	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).	Up to 6 months
Secondary	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	Up to 18 months
Secondary	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).	Up to 18 months
Secondary	Transplantation Rate Time Frame	Percentage of patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) during the study period.	Up to 18 months