Recruiting NCT07155226

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

Phase I / Phase II Interventional Acute Lymphoblastic Leukaemia Acute Myeloid Leukaemia Higher-risk Myelodysplastic Syndromes

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: AZD3632, Posaconazole.
Who it may be relevant to: Registry conditions: Acute Lymphoblastic Leukaemia, Acute Myeloid Leukaemia, Higher-risk Myelodysplastic Syndromes. Basic parameters: from 16 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Canada, Denmark, Germany +4
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Detailed description

This is a first in human (FTiH), open-label, multi-centre study of AZD3632 in participants with relapsed or refractory acute leukaemia or myelodysplastic Syndromes (MDS) with HOX overexpression genotypes.

This study includes multiple modules (module 1 and module 2) each investigating AZD3632 in a specific population and/or in combination with other anticancer agents.

Module 1 is a dose escalation of AZD3632 monotherapy. Module 2 will investigate the safety, PK, and tolerability when co-administered with posaconazole.

Interventions

Drug AZD3632
AZD3632 will be administered orally.
Drug Posaconazole
Posaconazole will be administered orally.

Primary outcome measures

Module 1: Number of participants with dose-limiting toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
Module 1 and Module 2: Number of participants with dose modification, delay and discontinuations due to adverse events (AEs) [Time frame: Up to 3 years 1 month]
Module 1 and Module 2: Number of participants with treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs) and serious adverse vents (SAEs) [Time frame: Up to 30 days after last dose (approximately 3 years 1 month)]

Secondary outcome measures (12)

Module 1 and Module 2: Maximum concentration (Cmax) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1 and Module 2: Time of maximum concentration (Tmax) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Trough concentration (Ctrough) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Area under the plasma concentration-time Curve from Time Zero to Infinity (AUC[inf]) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1 and Module 2: Area under the curve from time 0 to the time of last measurable concentration (AUC[0-t]) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Area under concentration-time curve in the dosing interval (AUCtau) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Apparent total body clearance (CL/F) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Apparent volume of distribution based on the terminal phase (VZ/F) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Half-life (t1/2) of AZD3632 [Time frame: From Day 1 to 3 years 1 month]
Module 1: Maximum concentration (Cmax) of AZD3632 (food effect) [Time frame: From Day 1 to 3 years 1 month]
Module 1: Time of maximum concentration (Tmax) of AZD3632 (food effect) [Time frame: From Day 1 to 3 years 1 month]
Module 1 and Module 2: Area under the curve from time 0 to the time of last measurable concentration (AUC[0-t]) of AZD3632 (food effect) [Time frame: From Day 1 to 3 years 1 month]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Non-randomized
Model: Sequential
Masking: Open label
Primary purpose: Treatment

Study locations

United States · 6 centers

Research Site — Decatur
Research Site — New York
Research Site — Chapel Hill
Research Site — Durham
Research Site — Portland
Research Site — Houston

Germany · 6 centers

Research Site — Dresden
Research Site — Frankfurt A. Main
Research Site — Halle
Research Site — Heidelberg
Research Site — München
Research Site — Ulm

United Kingdom · 5 centers

Research Site — Edinburgh
Research Site — London
Research Site — London
Research Site — Manchester
Research Site — Newcastle

Japan · 3 centers

Research Site — Bunkyō City
Research Site — Kashiwa
Research Site — Okayama

South Korea · 3 centers

Research Site — Seoul
Research Site — Seoul
Research Site — Seoul

Australia · 2 centers

Research Site — Fitzroy
Research Site — Perth

Canada · 2 centers

Research Site — Toronto
Research Site — Montreal

Italy · 2 centers

Research Site — Bologna
Research Site — Ravenna

Denmark · 1 center

Research Site — Copenhagen

Identifiers

NCT: NCT07155226 · D8620C00001 · 2025-521299-76-00

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗