Home
Clinical Trials
NCT06366789

Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated or Spliceosome Mutated Relapsed or Refractory Acute Myeloid Leukemia

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-29

Study Completion Date

2027-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a clinical study aiming to assess pharmacokinetics, pharmacodynamics and preliminary efficacy of ZE46-0134 in patients with FLT3 and spliceosome mutated Relapsed or Refractory Acute Myeloid Leukemia

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a Phase 1, open-label, multicenter, dose escalation, and dose optimization study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of ZE46-0134 in adult patients with relapsed or refractory AML with FLT3-ITD and/or FLT3-TKD mutations and spliceosome mutations. Patients with AML that are out-patients or hospitalized due to their AML can be enrolled in the study.

The study will be run in 2 parts: Part 1 will be dose escalation and determination of MTD, and Part 2 will be dose expansion.

Part 1 of the study will have 2 groups. Group 1: 3 to 6 eligible patients with FLT3 mutation will be sequentially enrolled into each of 8 planned dose level cohorts. Patients will receive up to 24 cycles (28 days each) of study treatment. For patients that continued to derive benefit after 24 cycles of treatment, continuation of ZE46-0134 therapy will be considered. Group 2: 3 to 6 eligible patients with spliceosome mutation will be sequentially enrolled into each of 4 planned dose level cohorts. Patients will receive up to 24 cycles (28 days each) of study treatment. For patients that continued to derive benefit after 24 cycles of treatment, continuation of ZE46-0134 therapy will be considered.

In Part 2, the dose expansion phase will involve enrolling up to 30 patients across 2 dose cohorts (i.e., 15 patients per cohort) for Group 1 and up to 30 patients across 2 dose cohorts (i.e., 15 patients per cohort) for Group 2. ZE46-0134 will be dosed as described for Part 1 of the study. The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study.

Indication background information:

Acute myeloid leukemia (AML) comprises a heterogeneous group of aggressive blood cell cancers that arise from clonal expansion of malignant hematopoietic precursor cells in the bone marrow (BM) and is the most commonly diagnosed adult leukemia with a median age at diagnosis is 68 years, with an overall survival (OS) rate of 29.8%. As patients age, there is a 10% decrease in 5-year OS for every additional decade of life, with a 5-year OS of 0.4% in patients age \>85 years1. Furthermore, remission rates and OS depend on a number of other factors, including cytogenetics, previous BM disorders, and comorbidities.

FMS-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase (RTK) primarily expressed on immature hematopoietic progenitors and hematopoietic stem cells. FLT3 signaling is initiated when FLT3 ligand binds to FLT3, inducing the dimerization and activation of FLT3 via autophosphorylation. This then activates downstream signaling of phosphoinositide 3-kinase/protein kinase B (PI3K/PKB), mitogen-activated protein kinase (MAPK), and JAK2/STAT5 which leads to cell proliferation and suppression of apoptosis2.

FLT3 kinase is directly implicated in the pathogenesis of hematologic malignancies, particularly AML. FLT3 mutations are the most frequently identified mutations in AML patients. Activating mutations in FLT3, which are FLT3-internal tandom duplication (ITD) and FLT3 tyrosine kinase domain (TKD) mutations, account for 30% of all AML cases2. As a result of these mutations, the FLT3 receptor is continuously activated leading to the continuous activation of downstream signaling pathways, PI3K/AKT, MAPK, and signal transducer and activator of transcription (STAT5), resulting in increased cell proliferation and decreased apoptosis.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

AML With Gene Mutations

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

dose escalation and dose optimization study

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

ZE46-0134 Dose Level -1

Optional and would only be performed Dose Level 1 is poorly tolerated

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study and will not exceed a loading dose of 150 mg x 2 days and maintenance dose of 50 mg QD

Group Type EXPERIMENTAL

ZE46-0134

Intervention Type DRUG

oral capsules QD

ZE46-0134 Selected dose 2

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study and will not exceed a loading dose of 150 mg x 2 days and maintenance dose of 50 mg QD

Optional and would only be performed Dose Level 1 is poorly tolerated

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study.

Group Type EXPERIMENTAL

ZE46-0134

Intervention Type DRUG

oral capsules QD

ZE50-0134 (Group 2) Selected dose 2

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study.

Group Type EXPERIMENTAL

ZE46-0134

Intervention Type DRUG

oral capsules QD

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

ZE46-0134

oral capsules QD

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Exclusion Criteria

1. Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Patient is ≥18 years of age at the time of obtaining informed consent.
3. Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
4. Patient must have a confirmed FLT3 ITD, TKD or ITD-F691L mutation documented within the past 90 days in absence of therapy or within the Screening period 28 days) prior to study drug administration on C1D1 if therapy has been given.
5. Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.
6. Patients have a life expectancy of at least 3 months in the opinion of the Investigator.
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
8. Patient must meet the following criteria as indicated on the clinical laboratory tests:

1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)
2. Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease
3. Estimated glomerular filtration (eGFR) rate of \>50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
9. Female patients:

1. If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
2. If of childbearing potential, must:

i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.

ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 45 days after the last dose of study drug.

iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from Screening until at least 45 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle).
10. Male patients and their female spouse/partners who are of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control (at least 1of which must be a barrier method) starting at Screening and continue throughout the study period and for 45 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 45 days after the final study drug administration.

1. Diagnosis of isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML)
2. Acute promyelocytic leukemia (FAB M3)
3. Active central nervous system (CNS) involvement by AML
4. Clinical signs/symptoms of leukostasis requiring urgent therapy
5. Known active infection with Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C. Patients with a history of positive serology for hepatitis B or C require a negative Polymerase chain reaction (PCR) test for virus to go onto therapy
6. Disseminated intravascular coagulopathy with active, unmanageable bleeding or signs of thrombosis.
7. Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent; if the half-life of the agent is unknown, patients must wait 1 week prior to first dose of study treatment. An investigational agent is one for which there is no approved indication by the local regulatory authority.
8. Systemic antineoplastic therapy within 5 half-lives or radiation therapy within 1 week prior to starting protocol with the exception of hydroxyurea, which is allowed to control white blood cell counts.
9. Female patients who are pregnant or lactating
10. Patients with psychological, familial, social, or geographic factors, other significant medical condition, laboratory abnormality that otherwise preclude them from giving informed consent, following the protocol, potentially hamper compliance with study treatment and follow-up or would confound the interpretation of the results of the study.
11. Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction with evidence of residual abnormalities within 6 months prior to enrollment (Troponin (regular or high sensitivity) leak alone not included if no residual dysfunction), New York Heart Association (NYHA) Class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled.
12. Infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control in the opinion of the Investigator. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Carolyn Grove, Prof

Role: PRINCIPAL_INVESTIGATOR

Linear Clinical Research

Review the countries where the study has at least one active or historical site.

ZE46-0134-0002

Identifier Type: -

Identifier Source: org_study_id

Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated or Spliceosome Mutated Relapsed or Refractory Acute Myeloid Leukemia

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Study Design

Study Groups

ZE46-0134 Dose Level -1

ZE46-0134

ZE46-0134 Dose Level 1

ZE46-0134

ZE46-0134 Dose Level 2

ZE46-0134

ZE46-0134 Dose Level 3

ZE46-0134

ZE46-0134 Dose Level 4

ZE46-0134

ZE46-0134 Dose Level 5

ZE46-0134

ZE46-0134 Selected dose 1

ZE46-0134

ZE46-0134 Selected dose 2

ZE46-0134

ZE46-0134 Dose Level 6

ZE46-0134

ZE46-0134 Dose Level 7

ZE46-0134

ZE46-0134 Dose Level 8

ZE46-0134

ZE50-0134 (Group 2) Dose Level -1

ZE46-0134

ZE50-0134 (Group 2) Dose Level 1

ZE46-0134

ZE50-0134 (Group 2) Dose Level 2

ZE46-0134

ZE50-0134 (Group 2) Dose Level 3

ZE46-0134

ZE50-0134 (Group 2) Dose Level 4

ZE46-0134

ZE50-0134 (Group 2) Selected dose 1

ZE46-0134

ZE50-0134 (Group 2) Selected dose 2

ZE46-0134

Interventions

ZE46-0134

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Lomond Therapeutics Holdings, Inc.

Responsible Party

Principal Investigators

Carolyn Grove, Prof

Locations

University of California, Los Angeles

University of California, San Francisco

Emory University

The University of Chicago

University of Kansas

University of Maryland

Memorial Sloan Kettering Cancer Center

University of North Carolina

University of Cincinnati

The Ohio State University

Oregon Health & Science University

The University of Texas Southwestern Medical Center

The Alfred Hospital

Eastern Health - Box Hill Hospital

Linear Clinical Research Ltd

Gachon University Gil Medical Center

Korea University Anam Hospital

Seoul National University Hospital

The Catholic University of Korea Seoul St. Mary's Hospital

Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare

China Medical University Hospital

National Cheng Kung University Hospital

Taichung Veterans General Hospital

Countries

Central Contacts