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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory
• Intervention / Treatment: Drug: Iadademstat; Drug: Gilteritinib Oral Tablet

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sonia Gutiérrez, MSc; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com
• Study Contact Backup: Name: Mónica Reale-Vidal, MD; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
      • Contact: Rajneesh Nath, MD; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com
    • Tucson, Arizona, United States, 85724-5024
      • Recruiting
      • The University of Arizona Cancer Center - North Campus
      • Contact: Sharad Khurana, MD, MSc; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
      • Principal Investigator: Sharad Khurana, MD
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • Miami Cancer Institute
      • Contact: Guenther Koehne, MD, PhD; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com
    • Miami, Florida, United States, 33136
      • Recruiting
      • Sylvester Comprehensive Cancer Center
      • Contact: Sangeetha Venugopal, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
  • Maryland
    • Baltimore, Maryland, United States, 21287-0013
      • Recruiting
      • The John Hopkins University School of Medicine
      • Contact: Alexander J Ambiender, MD; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital (MGH)
      • Contact: Amir Fathi, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
  • New Jersey
    • Piscataway, New Jersey, United States, 08854
      • Recruiting
      • Rutgers, the State University
      • Contact: Neil D Palmisiano, MD, MS; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital
      • Contact: Jonathan Feld, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
      • Contact: Harry P Erba, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Theodore P Braun, MD PhD; Phone Number: +34 935151313; Email: FRIDA_queries@oryzon.com
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute, LLC
      • Contact: Stephen Strickland, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University
      • Contact: Konstantinos Sdrimas, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital & the Medical College of Wisconsin
      • Contact: Guru SG Murthy, MD; Phone Number: +34935151313; Email: FRIDA_queries@oryzon.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm; iadademstat and gilteritinib	Drug: Iadademstat; iadademstat oral solution; Other Names: ORY-1001, RO7051790; Drug: Gilteritinib Oral Tablet; 120 mg Gilteritinib; Other Names: XOSPATA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE)	Number of participants with Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.	Up to 18 months
Laboratory value abnormalities and/or adverse events (AE)	Number of participants with laboratory value abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.	Up to 18 months
Vital sign abnormalities and/or adverse events (AEs)	Number of participants with vital signs abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.	Up to 18 months
Routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)	Number of participants with Routine 12-lead electrocardiogram (ECG )abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.	Up to 18 months
Recommend Phase 2 dose (RP2D)	Determine the recommended Phase 2 dose (RP2D) of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R	Up to 18 months
iadademstat tmax	Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.	Up to 26 days
Iadademstat Cmax	Measurement of the highest concentration of iadademstat in the blood after a dose is given.	Up to 26 days
iadademstat Cmin	Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.	Up to 26 days
iadademstat AUC	Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.	Up to 26 days
OR rate	Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).	Up to 18 months
iadademstat Target Engagement (TE)	Percent of drug covalently bound to LSD1 molecule	Up to 26 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from start of treatment to the time of death from any cause.	Up to 24 months
Event-Free-Survival (EFS)	Time from start of treatment to the date of failure to achieve CR or CRi, relapse from CR/CRi, or death from any cause, whichever occurs first.	Up to 18 months
Overall response rate	Percentage of patients with complete remission (CR), CR with incomplete blood count recovery (CRi), or PR.	Up to 6 months
Time to Response (TTR)	Time from the date of initial dosing at RP2D/expansion dose to first documentation of either a type of CR or Partial Response (PR).	Up to 6 months
Duration of Remission (DoR)	Time from the date of first documentation of any type of remission to the date of first documentation of progression of remission for remitters	Up to 18 months
Transfusion independence rate	A patient is defined as red blood cell (RBC) and/or platelet-transfusion independent if he/she receives no RBC and/or platelet transfusions for a period of at least 8 weeks. Rate of transfusion independence is the percentage of patients who become RBC and/or platelet transfusion independent (from the number of patients transfusion dependent at baseline).	Up to 18 months
Transplantation Rate Time Frame	Percentage of patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) during the study period.	Up to 18 months

Collaborators and Investigators

• Sponsor: Oryzon Genomics S.A.
• Investigators: Study Chair: Mónica Reale-Vidal, MD, Oryzon Genomics

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia, FLT3 mut
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Gilteritinib
• Other Study ID Numbers: CL04-ORY-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No