A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)

NCT05756777 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 22-174
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

The researchers are doing this study to see if the combination of gilteritinib with ivosidenib or enasidenib is a safe and effective treatment for people with relapsed/refractory AML with FLT3/IDH1 or FLT3/IDH2 gene mutations. The researchers will also look for the highest dose of the combination of gilteritinib with ivosidenib or enasidenib that causes few or mild side effects. When the highest safe dose is found, they will test that dose in new groups of participants.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Gilteritinib; Ivosidenib; Enasidenib; FLT3/IDH1 Mutations; FLT3/IDH2 Mutations; 21-174

Outcome Measures

Primary Outcomes (2)

• Determine the maximum tolerated dose (MTD)

  These are derived based on Dose Limiting Toxicities (DLT) according to BOIN dose escalation methodology.

  1 year

• Adverse events /toxicities

  will be graded using CTCAE 5.0 and described by frequency, duration and severity of treatment-emergent, treatment-related, and serious adverse events.

  1 year

Secondary Outcomes (1)

• Clinical response

  1 year

Study Arms (2)

gilteritinib + ivosidenib (Cohort 1)

EXPERIMENTAL

Each patient will take the combination of gilteritinib/ ivosidenib (Cohort 1) , daily, in continuous 28-day cycles at the dose level that they are assigned.

Drug: Gilteritinib; Drug: Ivosidenib

gilteritinib + enasidenib (Cohort 2)

EXPERIMENTAL

Each patient will take the combination of gilteritinib/enasidenib (Cohort 2) daily, in continuous 28-day cycles at the dose level that they are assigned.

Drug: Gilteritinib; Drug: Enasidenib

Interventions

Gilteritinib DRUG

Dose level (-1) 80mg, (1) 120mg, (2) 120mg

gilteritinib + enasidenib (Cohort 2); gilteritinib + ivosidenib (Cohort 1)

Ivosidenib DRUG

Dose level (-1) 250mg, (1) 250mg, (2) 500mg

gilteritinib + ivosidenib (Cohort 1)

Enasidenib DRUG

Dose level (-1) 50mg, (1) 50mg, (2) 100mg

gilteritinib + enasidenib (Cohort 2)

Eligibility Criteria

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

You may qualify if:

• Adult patient is ≥18 years of age at the time of signing the informed consent form (ICF)
• Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
• Patient has a confirmed diagnosis of relapsed AML as per World Health Organization (2016) guidelines. Patients in morphologic remission with the reappearance of MRD are also eligible to participate OR the patient has refractory AML as defined below:
• For patients who received intensive induction chemotherapy they must have persistent AML (defined as overt disease with over 5% myeloblasts) after at least one cycle of intensive induction OR
• For patients treated with low intensity therapy, the patient must be refractory to treatment with a single agent hypomethylating agent (HMA) or low dose cytarabine (LDAC) (at least two cycles) or an HMA/LDAC in combination with venetoclax (at least one cycle) or another standard of care therapy (e.g. gemtuzumab ozogamicin, glasdegib/LDAC).
• Patient has relapsed or refractory AML with dually mutant IDH2/FLT3, IDH1/FLT3 (ITD or TKD) , or other FLT3 mutation sensitive to gilteritinib.
• a. A Patient receiving enasidenib or ivosidenib as a single agent who acquires a FLT3 mutation during treatment or a patient on single agent gilteritinib who acquires an IDH2 or IDH1 mutation during treatment is eligible to participate in this study
• Patient has documentation of FLT3 and IDH1 or IDH2 mutation in bone marrow or blood at time of relapsed/refractory status confirmed by next-generation sequencing (NGS) and/or polymerase chain reaction (PCR) or fragment length analysis within the previous 30 days by a local CLIA approved test.
• Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
• Patient should have adequate renal function, defined as creatine clearance ≥30mL/min calculated using the Cockcroft-Gault equation or a serum creatinine less than 2.0.
• Patient should have adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x the upper limit of normal (ULN) and serum direct bilirubin ≤ 2.0 x ULN. Patient with leukemic organ involvement as assessed by the study investigator, must have a serum direct bilirubin ≤ 5.0 x ULN.
• Patient who has previously had an autologous or allogeneic stem cell transplant for AML is allowed on study.
• Female patient of childbearing potential must have had a negative pregnancy test within 7 days of initiation of dosing and must agree to use two acceptable methods of birth control while on treatment. A woman must agree to remain on a highly effective method throughout the study and for at least 6 months after the last dose of study drug. A female is considered fertile following menarche and until becoming postmenopausal unless permanently sterile.
• Male participants with female partners of childbearing potential are eligible for participation in the study if they agree to the following during treatment and until the end of relevant systemic exposure defined as 6 months after final drug administration.

You may not qualify if:

• Patient has a diagnosis of acute promyelocytic leukemia (APL).
• Patient on any other investigational anti-cancer agents.
• Patient has active uncontrolled systemic fungal, bacterial, or viral infection.
• Patient has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.
• Patient has immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or severe disseminated intravascular coagulation.
• Patient has significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or ischemic stroke.
• Patient has left ventricular ejection fraction (LVEF) \< 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.
• Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• Patient has a medical history of progressive multifocal leukoencephalopathy.
• Patient has QTc interval (i.e., Fridericia's correction \[QTcF\]) ≥ 450 ms (mean of triplicate ECG) or other factors that increase the risk of QT prolongation or ventricular arrhythmic events (e.g. family history of long QT interval syndrome). Patients with a QTcF over 450 ms due to a bundle branch block or a pacemaker may participate in the study with approval of the study principal investigator.
• Patient has active graft-versus-host disease. However patients with isolated skin GVH controlled with topical steroids are eligible to participate
• Female patient who is pregnant or lactating.

Sponsors & Collaborators

• Astellas Pharma US, Inc.: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk-Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; ivosidenib; enasidenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Eytan Stein, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eytan Stein, MD

CONTACT

646-608-3749; steine@mskcc.org

Aaron Goldberg, MD,PhD

CONTACT

646-608-3752

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: March 6, 2023
• Study Start: June 26, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)