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A Modular Phase I/II, Open-label, Multi-Centre Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Acute Lymphoblastic Leukaemia/Acute Myeloid Leukaemia/Higher-risk Myelodysplastic Syndromes
Date of first enrollment	12/01/2026
Target sample size	7
Countries of recruitment	Australia,Japan,Canada,Japan,Denmark,Japan,Germany,Japan,Italy,Japan,South Korea,Japan,United Kingdom,Japan,United States,Japan
Study type	Interventional
Intervention(s)	Module 1: AZD3632 will be administered orally. Module 2: AZD3632 will be administered orally. Posaconazole will be administered orally.

Outcome(s)

Primary Outcome

Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed. - Module 1: Number of participants with dose-limiting toxicity (DLT) - Module 1 and Module 2: Number of participants with dose modification, delay and discontinuations due to adverse events (AEs) - Module 1 and Module 2: Number of participants with treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs) and serious adverse vents (SAEs) Adverse events will be defined as treatment-emergent if they have an onset or worsen (by investigator report of a change in intensity) during the study treatment or the safety follow-up period but prior to any subsequent cancer therapy.

Secondary Outcome

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	Core criteria: - Adequate organ function. - Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Module 1: - Advanced haematologic malignancy - a) for dose escalation - diagnosis of acute leukemia or myelodysplastic neoplasia (MDS) and harbouring one of the genetic alterations per local testing associated with upregulation of HOX; b) for Backfill - diagnosis of harbouring a KMT2Ar or NPM1m per local testing. - Participants must have relapsed/refractory (R/R) and measurable disease: a) Relapsed and refractory (R/R) acute leukaemia after standard of care therapy including but not limited to 1 to 2 cycles of intensive chemotherapy or venetoclax combinations; b) R/R MDS is defined by 5% blasts or more in the bone marrow and/or persistence of peripheral blasts after treatment with at least an HMA. Participants ineligible for the treatment with an HMA and without any other standard of care (SoC) options are allowed to enrol; c) White blood cell count below 25,000/uL. Participants may receive cytoreduction per protocol-specified criteria; d) Performance status: Eastern Cooperative Operative Group (ECOG) 2 or less Module 2: - Participants must have relapsed/refractory and measurable disease: a) R/R acute leukaemia after standard of care therapy including but not limited to 1 to 2 cycles of intensive chemotherapy or venetoclax combinations; b) R/R MDS is defined by 5% blasts or more in the bone marrow and/or persistence of peripheral blasts after treatment with at least an HMA. Participants ineligible for the treatment with an HMA and without any other SoC options are allowed to enrol; c) White blood cell count below 25,000/uL. Participants may receive cytoreduction per protocol-specified criteria; d) Performance status: ECOG 2 or less
Exclude criteria	Core criteria: - Participants with Burkitt lymphoma/leukaemia or Acute Promyelocytic Leukaemia. - Active testicular or active central nervous system (CNS) (> CNS1 or radiographic) involvement by leukaemia. - Unresolved treatment-related toxicities Grade 2 or more from prior therapy. - Abnormal levels of potassium or magnesium prior to first dose of AZD3632. Module 1: - Receipt of non-CNS radiation therapy within 2 weeks and of CNS radiation within 8 weeks of the first scheduled dose. - Receipt of any investigational or non-investigational anticancer agents, including non-biologic agents, biologic agents and/or prior treatment other menin inhibitors (backfill participants only). - For nested food effect participants - diagnosis of diabetes mellitus (Type I or Type II). Module 2: - Receipt of any non-investigational anticancer agents, including non-biologic agents and/or biologic agents or receipt of non-CNS or CNS radiation therapy. - Participants for whom treatment with posaconazole is contraindicated per the local prescribing information.