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 or Spliceosome mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/06/23
Investigators and Locations
Co-Principal Investigator
- Ming-Yu Lien 無
- Chi-Ching Chen 無
- 王幸婷 無
- 鄭富銘 無
- Che-Hung Lin 無
- 陳珈妤 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 蔡承志 無
- HUI-WEN LIU 無
- Wei-Hong Cheng 無
- 莊博雅 無
- TSU-YI CHAO 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- CHENG-HSIEN LIN 無
- PO-HSIEN LI 無
- Chieh-Lin Teng 無
- Tsung -Chih Chen 無
- 滕傑林 無
- 鄧齡喬 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Tsai-Yun Chen
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Acute myeloid leukemia
Objectives
This is a Phase 1, open-label, multicenter, dose-escalation and dose-optimization trial to evaluate the safety, tolerability, pharmacokinetic (PK), disease progression (PD), and preliminary efficacy of ZE46-0134 in adult patients with relapsed or refractory AML and FLT3-ITD and/or FLT3-TKD mutations. Outpatient or inpatient AML patients are eligible for this trial.
The trial will be conducted in two parts: Part 1 involves dose escalation and determination of the mean tolerated dose (MTD), and Part 2 involves dose expansion.
Primary Objective:
• To determine the maximum tolerated dose (MTD) or bioeffective dose (BED) of ZE46-0134 in adults with relapsed and refractory AML with FLT3 mutations.
Secondary Objective:
• To determine the safety and tolerability of ZE46-0134 in adults with relapsed and refractory AML with FLT3 mutations.
• Determine the pharmacokinetic characteristics of ZE46-0134 in adults with relapsed and refractory AML harboring FLT3 mutations.
• Determine the optimal composite complete response [complete response (CR)/complete response with hematologic improvement (CRh)/complete response with incomplete recovery of blood cell count (CRi)], CR, and overall response rate (ORR) (CR, CRh, CRi, morphologically free leukemia status [MLFS]) in adults with relapsed and refractory AML harboring FLT3 mutations over 6 cycles (or earlier), CR, and overall response rate (ORR).
• Determine the 1-year overall survival (OS) of patients treated with ZE46-0134.
• Determine the median duration of response (DOR) of patients treated with ZE46-0134.
• Determine the proportion of patients who undergo allogeneic stem cell transplantation (HSCT) after receiving ZE46-0134. Exploratory Objectives:
• To determine the pharmacodynamics (PD) of ZE46-0134 treatment by measuring changes in FLT3, STAT5, and mitogen-derived kinase (MAPK) phosphorylation, cytokines, and other potential biomarkers.
• To determine the ability of ZE46-0134 to eliminate FLT3 ITD or FLT3-TKD to an undetectable minimal residual disease (MRD) state.
• To determine the genomic characteristics of responding and non-responding patients, as well as patients who responded to ZE46-0134 treatment but subsequently relapsed.
Test Drug
Capsules
Active Ingredient
ZE46-0134
Dosage Form
130
Dosage
10 mg and 50 mg
Endpoints
Determine the maximum tolerated dose (MTD) or bioeffective dose (BED) of ZE46-0134 in adults with relapsed and refractory AML with FLT3 mutations.
Inclution Criteria
To be enrolled in this trial, patients must meet all of the following criteria:
1. Written participant consent (including discontinuation of prohibited medications, if applicable) must be obtained from the patient prior to any trial-related procedures.
2. The patient's age must be ≥18 years at the time of obtaining participant consent.
3. The patient has been unresponsive or relapsed after multiple treatments for AML (with or without HSCT) and has exhausted all reasonable treatments expected to provide benefit, unless the patient refuses or is ineligible for such treatments.
4. The patient must have a centrally confirmed FLT3-ITD or FLT3-TKD mutation.
5. The patient must have previously received Gilteritinib treatment without disease progression, or the trial administrator deems the patient ineligible for Gilteritinib treatment, or has opted not to receive Gilteritinib treatment.
6. The patient's life expectancy must be at least 3 months, according to the trial administrator.
7. The patient's East Coast Cancer Clinical Research Consortium (ECOG) performance status must be ≤2.
8. Patients must meet the following criteria as indicated by clinical laboratory testing:
a. Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × Upper Limit of Normal (ULN).
b. Serum total bilirubin ≤1.5 × ULN, except in cases of Gilbert's disease, in which case a maximum total bilirubin concentration of 4.0 mg/dL is acceptable.
c. Estimated glomerular filtration rate (eGFR) calculated using the kidney disease diet improvement formula >60 mL/min.
9. Female Patients:
a. If infertile, i.e., having undergone sterilization (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks prior to the screening follow-up visit, or amenorrhea (defined as the absence of menstruation for 12 months without other medical cause, and follicle-stimulating hormone (FSH) levels consistent with amenorrhea according to local laboratory guidelines), or
b. If fertile, must:
i. Have a negative serum pregnancy test at the screening follow-up visit and a negative urine pregnancy test on day 1 of hospital admission (before drug administration).
ii. Agree not to attempt pregnancy or donate eggs from the time of signing the consent form until 105 days after the last dose of the experimental drug.
iii. Agree to use appropriate contraception (defined as, unless it is solely same-sex relations or a lifestyle of absolute abstinence, the male partner must use condoms in conjunction with a highly effective method of contraception from the time of screening until the last dose of the experimental drug). 10. Male patients of fertility and their female partners must agree to use highly effective contraception, including at least one barrier method, from the start of screening, throughout the trial, and for 105 days after the final administration of the investigational drug. Male patients may not donate sperm from the start of screening, throughout the trial, and for 105 days after the final administration of the investigational drug.
1. Written participant consent (including discontinuation of prohibited medications, if applicable) must be obtained from the patient prior to any trial-related procedures.
2. The patient's age must be ≥18 years at the time of obtaining participant consent.
3. The patient has been unresponsive or relapsed after multiple treatments for AML (with or without HSCT) and has exhausted all reasonable treatments expected to provide benefit, unless the patient refuses or is ineligible for such treatments.
4. The patient must have a centrally confirmed FLT3-ITD or FLT3-TKD mutation.
5. The patient must have previously received Gilteritinib treatment without disease progression, or the trial administrator deems the patient ineligible for Gilteritinib treatment, or has opted not to receive Gilteritinib treatment.
6. The patient's life expectancy must be at least 3 months, according to the trial administrator.
7. The patient's East Coast Cancer Clinical Research Consortium (ECOG) performance status must be ≤2.
8. Patients must meet the following criteria as indicated by clinical laboratory testing:
a. Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × Upper Limit of Normal (ULN).
b. Serum total bilirubin ≤1.5 × ULN, except in cases of Gilbert's disease, in which case a maximum total bilirubin concentration of 4.0 mg/dL is acceptable.
c. Estimated glomerular filtration rate (eGFR) calculated using the kidney disease diet improvement formula >60 mL/min.
9. Female Patients:
a. If infertile, i.e., having undergone sterilization (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks prior to the screening follow-up visit, or amenorrhea (defined as the absence of menstruation for 12 months without other medical cause, and follicle-stimulating hormone (FSH) levels consistent with amenorrhea according to local laboratory guidelines), or
b. If fertile, must:
i. Have a negative serum pregnancy test at the screening follow-up visit and a negative urine pregnancy test on day 1 of hospital admission (before drug administration).
ii. Agree not to attempt pregnancy or donate eggs from the time of signing the consent form until 105 days after the last dose of the experimental drug.
iii. Agree to use appropriate contraception (defined as, unless it is solely same-sex relations or a lifestyle of absolute abstinence, the male partner must use condoms in conjunction with a highly effective method of contraception from the time of screening until the last dose of the experimental drug). 10. Male patients of fertility and their female partners must agree to use highly effective contraception, including at least one barrier method, from the start of screening, throughout the trial, and for 105 days after the final administration of the investigational drug. Male patients may not donate sperm from the start of screening, throughout the trial, and for 105 days after the final administration of the investigational drug.
Exclusion Criteria
To be included in this trial, patients must not meet any of the following criteria:
1. Diagnosis of solitary myeloma (i.e., the patient must have AML hematologic or bone marrow involvement).
2. Acute promyelocytic leukemia (FAB M3).
3. Active AML central nervous system (CNS) involvement.
4. Clinical signs/symptoms of leukemia requiring urgent treatment.
5. Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Patients with a history of serologically positive hepatitis B or C must have a negative polymerase chain reaction (PCR) viral test to receive treatment.
6. Disseminated intravascular coagulation (DIC) with signs of active, uncontrollable bleeding or thrombosis.
7. Patients who have received an investigational drug (for any indication) within 5 half-lives of the drug; if the drug's half-life is unknown, patients must wait 1 week before the first dose of the investigational treatment. The investigational drug is one for which no indication has yet been approved by the local regulatory agency.
8. Patients who have received systemic chemotherapy or radiation therapy within 1 week prior to starting the treatment regimen, except for hydroxyurea, which allows for control of white blood cell counts.
9. Pregnant or breastfeeding female patients.
10. Patients with QTcF >470 msec that cannot be corrected by electrolyte replacement, rehydration, or medication.
11. Patients with psychological, familial, social, or geographical factors, other significant medical conditions, or laboratory abnormalities that prevent them from obtaining consent according to the trial protocol, may hinder trial treatment and follow-up adherence, or may obscure the interpretation of trial results.
12. Patients with the following conditions will be excluded: uncontrolled comorbidities within the 6 months prior to enrollment, including but not limited to: symptomatic congestive heart failure, unstable angina, severe arrhythmia, residual abnormalities from myocardial infarction (excluding isolated troponin (general or hypersensitive) leakage if there is no residual functional impairment), NYHA class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or ECG showing acute ischemia or active conduction abnormalities. Patients with comorbidities that would impair safety assessment should not be enrolled.
13. Infection is a common feature of AML. Patients with active infections may be allowed to participate if the trial administrator deems the infection under control. Patients with uncontrolled infections will not be enrolled until the infection has been treated and controlled.
1. Diagnosis of solitary myeloma (i.e., the patient must have AML hematologic or bone marrow involvement).
2. Acute promyelocytic leukemia (FAB M3).
3. Active AML central nervous system (CNS) involvement.
4. Clinical signs/symptoms of leukemia requiring urgent treatment.
5. Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Patients with a history of serologically positive hepatitis B or C must have a negative polymerase chain reaction (PCR) viral test to receive treatment.
6. Disseminated intravascular coagulation (DIC) with signs of active, uncontrollable bleeding or thrombosis.
7. Patients who have received an investigational drug (for any indication) within 5 half-lives of the drug; if the drug's half-life is unknown, patients must wait 1 week before the first dose of the investigational treatment. The investigational drug is one for which no indication has yet been approved by the local regulatory agency.
8. Patients who have received systemic chemotherapy or radiation therapy within 1 week prior to starting the treatment regimen, except for hydroxyurea, which allows for control of white blood cell counts.
9. Pregnant or breastfeeding female patients.
10. Patients with QTcF >470 msec that cannot be corrected by electrolyte replacement, rehydration, or medication.
11. Patients with psychological, familial, social, or geographical factors, other significant medical conditions, or laboratory abnormalities that prevent them from obtaining consent according to the trial protocol, may hinder trial treatment and follow-up adherence, or may obscure the interpretation of trial results.
12. Patients with the following conditions will be excluded: uncontrolled comorbidities within the 6 months prior to enrollment, including but not limited to: symptomatic congestive heart failure, unstable angina, severe arrhythmia, residual abnormalities from myocardial infarction (excluding isolated troponin (general or hypersensitive) leakage if there is no residual functional impairment), NYHA class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or ECG showing acute ischemia or active conduction abnormalities. Patients with comorbidities that would impair safety assessment should not be enrolled.
13. Infection is a common feature of AML. Patients with active infections may be allowed to participate if the trial administrator deems the infection under control. Patients with uncontrolled infections will not be enrolled until the infection has been treated and controlled.
The Estimated Number of Participants
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Taiwan
12 participants
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Global
60 participants
