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

NCT05546580 · Oryzon Genomics S.A.
In plain English

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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
About this study
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.
Study design
Enrollment target: 50 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-11-14
Estimated completion: 2025-11-30
Last updated: 2024-07-29
Interventions
Drug: IadademstatDrug: Gilteritinib Oral Tablet
Primary outcomes
  • Adverse Events (AE) (Up to 18 months)
  • Laboratory value abnormalities and/or adverse events (AE) (Up to 18 months)
  • Vital sign abnormalities and/or adverse events (AEs) (Up to 18 months)
Sponsor
Oryzon Genomics S.A. · industry
Contacts & investigators
ContactMónica Reale-Vidal, MD · contact · FRIDA_queries@oryzon.com · +34 935151313
ContactSonia Gutiérrez, MSc · contact · FRIDA_queries@oryzon.com · +34 935151313
InvestigatorMónica Reale-Vidal, MD · study_chair, Oryzon Genomics
All locations (13)
Banner MD Anderson Cancer CenterRecruiting
Gilbert, Arizona, United States
The University of Arizona Cancer Center - North CampusRecruiting
Tucson, Arizona, United States
Sylvester Comprehensive Cancer CenterRecruiting
Miami, Florida, United States
Miami Cancer InstituteRecruiting
Miami, Florida, United States
The John Hopkins University School of MedicineRecruiting
Baltimore, Maryland, United States
Massachusetts General Hospital (MGH)Recruiting
Boston, Massachusetts, United States
Rutgers, The State UniversityRecruiting
Piscataway, New Jersey, United States
Icahn School of Medicine at Mount Sinai and Mount Sinai HospitalRecruiting
New York, New York, United States
Duke University Medical CenterRecruiting
Durham, North Carolina, United States
Oregon Health & Science UniversityRecruiting
Portland, Oregon, United States
Sarah Cannon Research Institute, LLCRecruiting
Nashville, Tennessee, United States
West Virginia UniversityRecruiting
Morgantown, West Virginia, United States
Froedtert Hospital & The Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+) · TrialPath