Clinical trial NCT05546580: Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia, in Relapse
Acute Myeloid Leukemia Refractory
Keywords: Acute Myeloid Leukemia, FLT3 mut
Lead sponsor: Oryzon Genomics S.A.
Sponsor class: INDUSTRY
First posted: 2022-09-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Escalation/extension open label study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Adverse Events (AE)
timeFrame: Up to 18 months
measure: Laboratory value abnormalities and/or adverse events (AE)
timeFrame: Up to 18 months
measure: Vital sign abnormalities and/or adverse events (AEs)
timeFrame: Up to 18 months
measure: Routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
timeFrame: Up to 18 months
measure: Recommend Phase 2 dose (RP2D)
timeFrame: Up to 18 months
measure: iadademstat tmax
timeFrame: Up to 26 days
measure: Iadademstat Cmax
timeFrame: Up to 26 days
measure: iadademstat Cmin
timeFrame: Up to 26 days
measure: iadademstat AUC
timeFrame: Up to 26 days
measure: iadademstat Target Engagement (TE)
timeFrame: Up to 26 days
measure: OR rate
timeFrame: Up to 18 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Event-Free-Survival (EFS)
timeFrame: Up to 18 months
measure: Overall response rate
timeFrame: Up to 6 months
measure: Time to Response (TTR)
timeFrame: Up to 6 months
measure: Duration of Remission (DoR)
timeFrame: Up to 18 months
measure: Transfusion independence rate
timeFrame: Up to 18 months
measure: Transplantation Rate Time Frame
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center - North Campus
state: Arizona
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Baltimore
country: United States
facility: The John Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH)
state: Massachusetts
city: Piscataway
country: United States
facility: Rutgers, The State University
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute, LLC
state: Tennessee
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital & The Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Oryzon Genomics
name: Mónica Reale-Vidal, MD
role: STUDY_CHAIR
References: