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

Oryzon Genomics

Status and phase

Enrolling

Phase 1

Conditions

Acute Myeloid Leukemia Refractory

Acute Myeloid Leukemia, in Relapse

Treatments

Drug: Gilteritinib Oral Tablet

Drug: Iadademstat

Study type

Interventional

Funder types

Industry

Identifiers

NCT05546580

CL04-ORY-1001

Details and patient eligibility

About

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.

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.