AZD3632, alone or with other anticancer agents, for advanced blood cancers driven by HOX overexpression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a first‑in‑human, open‑label, multi‑center study enrolling adults with relapsed or refractory acute leukaemia or higher‑risk myelodysplastic syndromes whose tumors show HOX overexpression genotypes. The program is organized into modules: module 1 performs dose escalation of AZD3632 as monotherapy, and module 2 studies safety, PK, and tolerability when AZD3632 is co‑administered with posaconazole. Key outcomes include safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti‑leukaemic activity. Participants must have measurable disease, adequate organ function, and relevant genetic alterations such as KMT2A rearrangements or NPM1 mutations.

Why it matters

Who can join: the full rules

Key Inclusion 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 measurable disease that is relapsed/refractory to conventional therapies known to be effective for their disease and not have any available approved therapies.: a) Relapsed and primary refractory acute leukaemia after standard of care therapy including but not limited to 2 cycles of intensive chemotherapy, hypomethylating agent (HMA) monotherapy, or HMA combinations such as HMA/venetoclax.; b) Relapsed and primary refractory MDS is defined by ≥ 5% blasts in the bone marrow and/or persistence of peripheral blasts after treatment with at least 2 cycles of 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/μL. Participants may receive cytoreduction per protocol-specified criteria; d) Performance status: Eastern Cooperative Operative Group (ECOG) ≤ 2; e) Life expectancy: ≥ 8 weeks.

Module 2:

* Participants must have measurable disease that is relapsed/refractory to conventional therapies known to be effective for their disease and not have any available approved therapies.: a) Relapsed and primary refractory acute leukaemia after standard of care therapy including but not limited to 2 cycles of intensive chemotherapy, HMA monotherapy, or HMA combinations such as HMA/venetoclax.; b) Relapsed and primary refractory MDS is defined by ≥ 5% blasts in the bone marrow and/or persistence of peripheral blasts after treatment with at least 2 cycles of 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/μL. Participants may receive cytoreduction per protocol-specified criteria; d) Performance status: ECOG ≤ 2; e) Life expectancy: ≥ 8 weeks.

Key Exclusion 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 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.

Where it's running

• Research Site
  Decatur, Illinois, United States Recruiting
• Research Site
  Durham, North Carolina, United States Recruiting
• Research Site
  Houston, Texas, United States Recruiting
• Research Site
  Copenhagen, Denmark Recruiting
• Research Site
  Dresden, Germany Recruiting
• Research Site
  Frankfurt A. Main, Germany Recruiting

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.