SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation

NCT06222580 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-23199NCI-2024-00036
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial tests the safety, side effects, and best dose of SNDX-5613 and gilteritinib for treating patients with acute myeloid leukemia that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and has a mutation in the FLT3 gene along with either a mutation in the NMP1 gene or a type of mutation called a rearrangement in the MLL gene. SNDX-5613 is in a class of medications called menin inhibitors. It works by blocking the action of mutated MLL and NMP1 proteins that signal cancer cells to multiply. Gilteritinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of mutated FLT3 proteins that signal cancer cells to multiply. Giving SNDX-5613 with gilteritinib may be safe, tolerable and/or effective in treating patients with relapsed/refractory FLT3 mutated acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With KMT2A Rearrangement; Acute Myeloid Leukemia With NPM1 Mutation; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Incidence of hematologic adverse events (AEs)

  Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The toxicity data captured will include type, frequency, grade, severity, timing of onset, duration and relationship to study drug. Frequency tables will be used to summarize the AE data, where the number of patients with different types of AE will be tabulated by toxicity grade, counting only the highest grade of a certain type of AE occurred to the same patient. All adverse events regardless of attribution as well as those treatment- related AEs will be summarized.

  Up to 30 days after completion of study treatment

• Incidence of non-hematologic adverse events

  Adverse events will be graded according to CTCAE v5.0. The toxicity data captured will include type, frequency, grade, severity, timing of onset, duration and relationship to study drug. Frequency tables will be used to summarize the AE data, where the number of patients with different types of AE will be tabulated by toxicity grade, counting only the highest grade of a certain type of AE occurred to the same patient. All adverse events regardless of attribution as well as those treatment- related AEs will be summarized.

  Up to 30 days after completion of study treatment

• Recommended phase 2 dose for drug combination

  Will be determined based on the maximum tolerated dose in conjunction with pharmacokinetic and pharmacodynamic assessments.

  During cycle 1 (28 days)

Secondary Outcomes (6)

• Composite Complete Response Rate (CRc)

  Up to 2 years

• Overall Response Rate

  Up to 2 years

• Rate of CRc with Measurable Residual Disease Negativity

  Up to 2 years

• Duration of response

  From the date of first response to the earliest documentation of progressive disease, relapsed disease, or death, up to 2 years

• Overall Survival

  From date of treatment start to death due to all cause, up to 2 years

Study Arms (1)

Treatment (SNDX-5613 and gilteritinib)

EXPERIMENTAL

Patients receive SNDX-5613 PO BID and gilteritinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA scan during screening, as well as bone marrow biopsy and aspiration and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Gilteritinib; Drug: Revumenib; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (SNDX-5613 and gilteritinib)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (SNDX-5613 and gilteritinib)

Gilteritinib DRUG

Given PO

Also known as: ASP-2215, ASP2215

Treatment (SNDX-5613 and gilteritinib)

Revumenib DRUG

Given PO

Also known as: Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613, Menin-MLL Inhibitor SNDX-5613, Menin-MLL Interaction Inhibitor SNDX-5613, SNDX 5613, SNDX-5613, SNDX5613

Treatment (SNDX-5613 and gilteritinib)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography, ECHO

Treatment (SNDX-5613 and gilteritinib)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood pool scan, Equilibrium Radionuclide angiography, Gated blood pool imaging, Gated heart pool scan, MUGA, MUGA Scan, Radionuclide ventriculogram scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA scanning, Synchronized multigated acquisition scanning, Multi-gated Acquistion Scan

Treatment (SNDX-5613 and gilteritinib)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Age ≥ 18 years at the date of signing the informed consent form (ICF)
• Morphologically confirmed diagnosis of the following based on 2022 World Health Organization (WHO) classification:
• Relapsed or Refractory Acute Myeloid Leukemia with the following:
• Refractory disease classified as having received 2 cycles of intensive induction or 2 cycles of hypomethylating agent (HMA) + Venetoclax with persistent disease of ≥ 5% blasts in the bone marrow and/or reappearance of peripheral blasts
• FLT-3 mutated disease of the ITD or TKD subtype, AND
• NPM1 mutation, MLL gene rearrangement and any other mutation that has proven HOXA-MEIS1 overexpression (NUP98, UBTF-TD, MLL-PTD and any others that have supporting literature)
• Patients must be receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis for at least 24 hours prior to enrollment and while on SNDX-5613 treatment. Patients must not be receiving any other strong CYP3A4 inhibitors/inducers
• Not suitable for immediate myeloablative/intensive chemotherapy based on investigator assessment of age, comorbidities, local guidelines, institutional practice (any or all of these)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 × ULN (except in the setting of isolated Gilbert syndrome)
• Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m\^2 (estimation based on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory)
• Adequate cardiac function defined as ejection fraction (EF) of ≥50% by echocardiogram or multigated acquisition (MUGA) scan
• Patient can communicate with the investigator and has the ability to comply with the requirements of the study procedures

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia
• Diagnosis of extra-medullary acute myeloid leukemia (AML) based on WHO 2022 classification or myeloid sarcoma
• Suspected central nervous system (CNS) involvement. Patients with history of cerebrospinal fluid (CSF) involvement must either have documented CSF clearance prior to treatment initiation or be receiving active treatment for CNS involvement
• Participants with prior malignancy, except:
• Participants with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study
• Participants who are receiving adjuvant therapy such as hormone therapy are eligible. However, participants who developed therapy related neoplasms are not eligible
• Previous known allergy/sensitivity to components of gilteritinib or SNDX-5613. Prior treatment with gilteritinib is allowed and does not exclude a patient
• Patient with known human immunodeficiency virus (HIV) or has active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Individuals with a history of HCV infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Fridericia's corrected QT interval (QTcF) \> 450 msec at time of screening
• Clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
• Uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 2 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure
• Patients with uncontrolled infection will not be enrolled until infection is treated and under control per the principal investigator or their designee
• Any psychiatric illness that prevents patient from informed consent process
• Pregnant or breastfeeding at the time of enrollment
• Patient has a malabsorption syndrome or other condition that precludes an enteral route of administration

Sponsors & Collaborators

• Uma Borate: lead

Study Sites (3)

UNC Hospitals, University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 24514, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Specimen Handling; Biopsy; gilteritinib; revumenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Uma M Borate, MD, MS

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 24, 2024
• Study Start: February 20, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)