Overview
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.
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.