Clinical Trials List
Protocol NumberZE46-0134-0002-US
Not yet recruiting
2025-07-07 - 2029-12-31
Phase I
Recruiting4
A Phase 1, Open-label, Dose Escalation and Dose Expansion, Multicenter Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ZE46-0134 in Adults with FLT3 mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
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Sponsor
Lomond Therapeutics AU Pty Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Che-Hung Lin 無
- Ming-Yu Lien 無
- Chi-Ching Chen 無
- 王幸婷 無
- 鄭富銘 無
- 陳珈妤 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chieh-Lin Teng 無
- 鄧齡喬 無
- Tsung -Chih Chen 無
- 滕傑林 無
- CHENG-HSIEN LIN 無
- PO-HSIEN LI 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 張力常 無
- 傅蓓安 無
- Ya-Ting Hsu 無
- Sin-Syue Li 無
- Ya-Ping Chen 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Yao-Yu Hsieh
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
FLT3 mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
Objectives
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. As we gain more knowledge about other alternative targets of ZE46-0134, we may expand this to other molecular groups.
The study will be run in 2 parts:
Part 1: will be dose escalation and determination of MTD of ZE46-0134. This part of the study will utilize a 3+3 design across 5 dose cohorts. Each cohort will have a maximum of 6 participants administered ZE46-0134.
Part 2: will be dose expansion of up to 2 dose cohorts with up to 15 participants in each cohort. ZE46-0134 doses for Part 2 will be determined based on review of the data from Part 1 of the study.
This is an accepted study design for Phase 1 oncology studies which aim to determine the MTD and R2PD.
Test Drug
capsul
Active Ingredient
ZE46-0134
Dosage Form
130
Dosage
10 mg and 50 mg
Endpoints
To determine the maximum tolerated dose (MTD) or biologically effective dose (BED) of ZE46-0134 in adults with FLT3 mutated relapsed and refractory AML
Inclution Criteria
1.
Written Informed Consent must be obtained from the patient 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 multiple AML therapies (with or without HSCT), and have exhausted all reasonable therapies expected to produce benefit unless the patient declines or is ineligible for these.
4.
Patient must have a confirmed FLT3-ITD or FLT3-TKD mutation by central laboratory testing.
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.
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:
a.
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN).
b.
Serum total bilirubin ≤1.5 × ULN unless due to Gilbert’s disease where a maximum total bilirubin level of 4.0 mg/dL is acceptable.
c.
Estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the Modification of Diet in Renal Disease equation.
9.
Female patients:
a.
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
b.
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 (pre-dose).
ii.
Agree not to attempt to become pregnant or donate ova from signing the consent form until 105 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 105 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 105 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 105 days after the final study drug administration.
Written Informed Consent must be obtained from the patient 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 multiple AML therapies (with or without HSCT), and have exhausted all reasonable therapies expected to produce benefit unless the patient declines or is ineligible for these.
4.
Patient must have a confirmed FLT3-ITD or FLT3-TKD mutation by central laboratory testing.
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.
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:
a.
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN).
b.
Serum total bilirubin ≤1.5 × ULN unless due to Gilbert’s disease where a maximum total bilirubin level of 4.0 mg/dL is acceptable.
c.
Estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the Modification of Diet in Renal Disease equation.
9.
Female patients:
a.
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
b.
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 (pre-dose).
ii.
Agree not to attempt to become pregnant or donate ova from signing the consent form until 105 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 105 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 105 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 105 days after the final study drug administration.
Exclusion Criteria
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 chemotherapy 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 QTcF > 470 msec that cannot be corrected with electrolyte replacement, hydration, or medication modifications.
11.
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.
12.
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.
13.
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.
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 chemotherapy 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 QTcF > 470 msec that cannot be corrected with electrolyte replacement, hydration, or medication modifications.
11.
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.
12.
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.
13.
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.
The Estimated Number of Participants
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Taiwan
12 participants
-
Global
60 participants
