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

NCT05546580 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CL04-ORY-1001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

Keywords

Acute Myeloid Leukemia, FLT3 mut

Outcome Measures

Primary Outcomes (11)

• 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

• iadademstat Target Engagement (TE)

  Percent of drug covalently bound to LSD1 molecule

  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

Secondary Outcomes (7)

• Overall Survival (OS)

  Up to 24 months

• Event-Free-Survival (EFS)

  Up to 18 months

• Overall response rate

  Up to 6 months

• Time to Response (TTR)

  Up to 6 months

• Duration of Remission (DoR)

  Up to 18 months

Study Arms (1)

Active arm

EXPERIMENTAL

iadademstat and gilteritinib

Drug: Iadademstat; Drug: Gilteritinib Oral Tablet

Interventions

Iadademstat DRUG

iadademstat oral solution

Also known as: ORY-1001, RO7051790

Active arm

Gilteritinib Oral Tablet DRUG

120 mg Gilteritinib

Also known as: XOSPATA®

Active arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oryzon Genomics S.A.: lead

Study Sites (13)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85724-5024, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

The John Hopkins University School of Medicine

Baltimore, Maryland, 21287-0013, United States

RECRUITING

Massachusetts General Hospital (MGH)

Boston, Massachusetts, 02114, United States

RECRUITING

Rutgers, The State University

Piscataway, New Jersey, 08854, United States

RECRUITING

Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27705, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Sarah Cannon Research Institute, LLC

Nashville, Tennessee, 37203, United States

RECRUITING

West Virginia University

Morgantown, West Virginia, 26506, United States

RECRUITING

Froedtert Hospital & The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

iadademstat; gilteritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Mónica Reale-Vidal, MD

  Oryzon Genomics

  STUDY CHAIR

Central Study Contacts

Mónica Reale-Vidal, MD

CONTACT

+34 935151313; FRIDA_queries@oryzon.com

Sonia Gutiérrez, MSc

CONTACT

+34 935151313; FRIDA_queries@oryzon.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Escalation/extension open label study

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 21, 2022
• Study Start: November 14, 2022
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: July 29, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)