Study 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
Posaconazole: Posaconazole will be administered orally.
Study summary
The purpose of this study is to understand the safety, tolerability, efficacy, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of orally administered AZD3632 in participants with advanced haematologic malignancies with KMT2Ar, NPM1m, or other genotypes associated with homeobox (HOX) overexpression.
Eligibility
Sex
ALL
Min age
16 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Module 1: Number of participants with dose-limiting toxicity (DLT) — At the end of Cycle 1 (each cycle is 28 days) Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.
Module 1 and Module 2: Number of participants with dose modification, delay and discontinuations due to adverse events (AEs) — Up to 3 years 1 month Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.
Module 1 and Module 2: Number of participants with treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs) and serious adverse vents (SAEs) — Up to 30 days after last dose (approximately 3 years 1 month) Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed. 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.
Trial sites (30)
Facility
City
Region
Status
Research Site
Decatur
Illinois
Recruiting
Research Site
New York
New York
Not Yet Recruiting
Research Site
Chapel Hill
North Carolina
Not Yet Recruiting
Research Site
Durham
North Carolina
Recruiting
Research Site
Portland
Oregon
Suspended
Research Site
Houston
Texas
Recruiting
Research Site
Fitzroy
Australia
Suspended
Research Site
Perth
Australia
Suspended
Research Site
Toronto
Ontario
Suspended
Research Site
Montreal
Quebec
Suspended
Research Site
Copenhagen
Denmark
Recruiting
Research Site
Dresden
Germany
Recruiting
Research Site
Frankfurt A. Main
Germany
Recruiting
Research Site
Halle
Germany
Recruiting
Research Site
Heidelberg
Germany
Recruiting
Research Site
München
Germany
Recruiting
Research Site
Ulm
Germany
Recruiting
Research Site
Bologna
Italy
Recruiting
Research Site
Ravenna
Italy
Recruiting
Research Site
Bunkyō City
Japan
Recruiting
Research Site
Kashiwa
Japan
Not Yet Recruiting
Research Site
Okayama
Japan
Recruiting
Research Site
Seoul
South Korea
Recruiting
Research Site
Seoul
South Korea
Recruiting
Research Site
Seoul
South Korea
Recruiting
Research Site
Edinburgh
United Kingdom
Recruiting
Research Site
London
United Kingdom
Recruiting
Research Site
London
United Kingdom
Recruiting
Research Site
Manchester
United Kingdom
Recruiting
Research Site
Newcastle
United Kingdom
Suspended
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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