study of iadademstat and gilteritinib in patients with r/r aml with fms-like tyrosine kinase mutation (flt3 mut+)

Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

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.

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.

Keywords: acute myeloid leukemia, flt3 mut