Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)
Purpose
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.
Conditions
- Acute Myeloid Leukemia, in Relapse
- Acute Myeloid Leukemia Refractory
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- Escalation/extension open label study
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Active arm |
iadademstat and gilteritinib |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Oryzon Genomics S.A.
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.