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

Recruiting now · Phase 1

Conditions studied: AML With Gene Mutations

In brief

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

Key facts

Study ID

NCT06366789

Run by

Lomond Therapeutics Holdings, Inc.

People needed

150

Starts

2024-05-29

Expected to finish

2027-12-01

Last updated by the study team

2025-12-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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).
• Patient is ≥18 years of age at the time of obtaining informed consent.
• Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
• Group 1: Patient must have a confirmed FLT3-ITD or FLT3-TKD mutation by central laboratory testing. Group 2: Patient must have a documented SF3B1, SRSF2, U2AF1, or ZRSR2 pathogenic mutation by local lab sequencing.
• For Group 1 only: 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.
• Patients have a life expectancy of at least 3 months in the opinion of the Investigator.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Patient must meet the following criteria as indicated on the clinical laboratory tests:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)
• Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease
• Estimated glomerular filtration (eGFR) rate of >50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Female patients:
• 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
• 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).
• 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.

You may not qualify if…

• 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).
• Patient is ≥18 years of age at the time of obtaining informed consent.
• Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
• 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.
• 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.
• Patients have a life expectancy of at least 3 months in the opinion of the Investigator.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Patient must meet the following criteria as indicated on the clinical laboratory tests:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)
• Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease
• Estimated glomerular filtration (eGFR) rate of >50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Female patients:
• 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
• 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).
• 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.
• Exclusion criteria
• Diagnosis of isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML)
• Acute promyelocytic leukemia (FAB M3)
• Active central nervous system (CNS) involvement by AML
• Clinical signs/symptoms of leukostasis requiring urgent therapy
• 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
• Disseminated intravascular coagulopathy with active, unmanageable bleeding or signs of thrombosis.

Where it is running

• University of California, Los Angeles — Los Angeles, California, United States (enrolling)
• University of California, San Francisco — San Francisco, California, United States (enrolling)
• Emory University — Atlanta, Georgia, United States (enrolling)
• The University of Chicago — Chicago, Illinois, United States (enrolling)
• University of Kansas — Lawrence, Kansas, United States (enrolling)
• University of Maryland — College Park, Maryland, United States (enrolling)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• University of North Carolina — Chapel Hill, North Carolina, United States (enrolling)
• University of Cincinnati — Cincinnati, Ohio, United States (enrolling)
• The Ohio State University — Columbus, Ohio, United States (enrolling)
• Oregon Health & Science University — Portland, Oregon, United States (enrolling)
• The University of Texas Southwestern Medical Center — Dallas, Texas, United States (enrolling)
• The Alfred Hospital — Melbourne, Victoria, Australia (enrolling)
• Eastern Health - Box Hill Hospital — Melbourne, Victoria, Australia (enrolling)
• Linear Clinical Research Ltd — Perth, Western Australia, Australia (enrolling)
• Gachon University Gil Medical Center — Incheon, Gyeonggi-do, South Korea
• Korea University Anam Hospital — Seoul, South Korea
• Seoul National University Hospital — Seoul, South Korea
• The Catholic University of Korea Seoul St. Mary's Hospital — Seoul, South Korea
• Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare — New Taipei City, Taiwan
• China Medical University Hospital — Taichung, Taiwan
• National Cheng Kung University Hospital — Tainan, Taiwan
• Taichung Veterans General Hospital — Xitun, Taiwan

Full record on ClinicalTrials.gov

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