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

NCT ID: NCT07155226

Last Updated: 2026-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-09

Study Completion Date

2029-02-15

Brief Summary

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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

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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.

Conditions

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Acute Lymphoblastic Leukaemia Acute Myeloid Leukaemia Higher-risk Myelodysplastic Syndromes

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Module 1: AZD3632 dose 1

Participants will receive AZD3632 (dose 1) through the treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Module 1: AZD3632 dose 2

Participants will receive AZD3632 (dose 2) through the treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Module 1: AZD3632 dose 3

Participants will receive AZD3632 (dose 3) through the treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Module 1: AZD3632 dose 4

Participants will receive AZD3632 (dose 4) through the treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Module 1: AZD3632 dose 5

Participants will receive AZD3632 (dose 5) through the treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Module 1: AZD3632 dose 6

Participants will receive AZD3632 (dose 6) through the treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Module 2: AZD3632 + posaconazole

Participants will receive AZD3632 alone, then will receive AZD3632 in combination with posaconazole through treatment period.

Group Type EXPERIMENTAL

AZD3632

Intervention Type DRUG

AZD3632 will be administered orally.

Posaconazole

Intervention Type DRUG

Posaconazole will be administered orally.

Interventions

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AZD3632

AZD3632 will be administered orally.

Intervention Type DRUG

Posaconazole

Posaconazole will be administered orally.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Research Site

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Research Site

Manchester, , United Kingdom

Site Status RECRUITING

Research Site

Newcastle, , United Kingdom

Site Status NOT_YET_RECRUITING

Research Site

Decatur, Illinois, United States

Site Status NOT_YET_RECRUITING

Research Site

New York, New York, United States

Site Status NOT_YET_RECRUITING

Research Site

Durham, North Carolina, United States

Site Status NOT_YET_RECRUITING

Research Site

Portland, Oregon, United States

Site Status NOT_YET_RECRUITING

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Fitzroy, , Australia

Site Status NOT_YET_RECRUITING

Research Site

Perth, , Australia

Site Status NOT_YET_RECRUITING

Research Site

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Research Site

Montreal, Quebec, Canada

Site Status NOT_YET_RECRUITING

Research Site

Copenhagen, , Denmark

Site Status NOT_YET_RECRUITING

Research Site

Dresden, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Frankfurt A. Main, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Halle, , Germany

Site Status RECRUITING

Research Site

Heidelberg, , Germany

Site Status NOT_YET_RECRUITING

Research Site

München, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Ulm, , Germany

Site Status RECRUITING

Research Site

Bologna, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Ravenna, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Bunkyō City, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Kashiwa, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Okayama, , Japan

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

Research Site

Edinburgh, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada Denmark Germany Italy Japan South Korea United Kingdom

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

Other Identifiers

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2025-521299-76-00

Identifier Type: OTHER

Identifier Source: secondary_id

D8620C00001

Identifier Type: -

Identifier Source: org_study_id

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