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AZD3632 for Advanced Hematologic Malignancies with HOX Overexpression

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Study AimThis study aims to evaluate the safety and tolerability of AZD3632 in adults with advanced blood cancers that have HOX gene overexpression.
What is being tested

AZD3632

+ Posaconazole
Drug
Who is being recruted

Acute Lymphoblastic Leukaemia

+ Acute Myeloid Leukaemia
+ Higher-risk Myelodysplastic Syndromes
Over 16 Years
+14 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: November 2025

See protocol details

Summary

Principal SponsorAstraZeneca
Study ContactAstraZeneca Clinical Study Information Center
Last updated: September 4, 2025
Sourced from a government-validated database.Claim as a partner
Study start date: November 3, 2025Actual date on which the first participant was enrolled.

This clinical trial is focused on testing a new medication called AZD3632 for individuals with advanced blood cancers like relapsed or resistant acute leukemia or myelodysplastic syndromes (MDS), specifically those with certain genetic markers linked to HOX overexpression. The aim is to assess the safety and effectiveness of this drug, either on its own or combined with other cancer treatments. This research is essential as it seeks to discover better treatment options for patients with these challenging conditions, where current therapies may not work effectively. Participants in the study will receive AZD3632, with some receiving just this medication, while others will have it combined with another drug, posaconazole. The study will begin by determining the right dosage of AZD3632 to ensure it is safe and well-tolerated. Researchers will closely monitor participants to measure how the body processes the drug and its effects on the cancer. Through these steps, the study aims to gather vital information on the drug's safety profile and its potential benefits in treating these specific blood cancers.

Official TitleA 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 
Principal SponsorAstraZeneca
Study ContactAstraZeneca Clinical Study Information Center
Last updated: September 4, 2025
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
84 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are assigned to groups based on specific criteria, such as their medical history or a doctor's recommendation. This approach ensures that treatments are given to those who may benefit the most, based on known factors.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants receive treatments one after another in a pre-planned sequence. The next treatment may depend on how the participant responds to the previous one.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 16 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Acute Lymphoblastic Leukaemia
Acute Myeloid Leukaemia
Higher-risk Myelodysplastic Syndromes
Criteria
5 inclusion criteria required to participate
Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
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.
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.

Show More Criteria

9 exclusion criteria prevent from participating
Unresolved treatment-related toxicities Grade ≥ 2 from prior therapy.
Participants for whom treatment with posaconazole is contraindicated per the local prescribing information.
Active testicular or active central nervous system (CNS) (\> CNS1 or radiographic) involvement by leukaemia.
Participants with Burkitt lymphoma/leukaemia or Acute Promyelocytic Leukaemia.

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
7 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Participants will receive AZD3632 (dose 1) through the treatment period.
Group II
Experimental
Participants will receive AZD3632 (dose 2) through the treatment period.
Group III
Experimental
Participants will receive AZD3632 (dose 3) through the treatment period.
Group IV
Experimental
Participants will receive AZD3632 (dose 4) through the treatment period.
Group 5
Experimental
Participants will receive AZD3632 (dose 5) through the treatment period.
Group 6
Experimental
Participants will receive AZD3632 (dose 6) through the treatment period.
Group 7
Experimental
Participants will receive AZD3632 alone, then will receive AZD3632 in combination with posaconazole through treatment period.
Study Objectives
Primary Objectives

Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.

Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.

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.
Secondary Objectives

The PK of AZD3632 as monotherapy (module 1) and in combination with posaconazole (module 2) will be assessed.

The PK of AZD3632 as monotherapy (module 1) and in combination with posaconazole (module 2) will be assessed.

The PK of AZD3632 as monotherapy will be assessed.

The PK of AZD3632 as monotherapy will be assessed.

The PK of AZD3632 as monotherapy (module 1) and in combination with posaconazole (module 2) will be assessed.

The PK of AZD3632 as monotherapy will be assessed.

The PK of AZD3632 as monotherapy will be assessed.

The PK of AZD3632 as monotherapy will be assessed.

The PK of AZD3632 as monotherapy will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.

The PK pf AZD3632 when co-administered with posaconazole will be assessed.

The PK pf AZD3632 when co-administered with posaconazole will be assessed.

The PK pf AZD3632 when co-administered with posaconazole will be assessed.

Complete response rate is defined as the percentage of participants who have a complete remission (CR) or complete remission with partial haematological recovery (CRh) as assessed by the investigator at local site.

TTR in participants with acute leukaemia is defined as the time from date of first dose until date of first documented complete response (CR/CRh) among participants with acute leukaemia in the Response Evaluable Set who achieved complete response as assessed by investigator at local site. TTR in participants with MDS is defined as the time from date of first dose until date of first documented objective response a CR (or CR equivalent), complete response with limited count recovery \[CRL\], CRh, partial response \[PR\], or haematologic improvement \[HI\]) among participants with MDS in the Response Evaluable Set who achieved objective response as assessed by investigator at local site.

DoR in participants with acute leukaemia is defined as the time from date of first documented complete response (CR/CRh) until date of first documented relapse or death (by any cause in the absence of relapse) as assessed by investigator at local site. DoR in participants with MDS is defined as the time from date of first documented objective response CR (or CR equivalent), CRL, CRh, PR, or HI until date of first documented relapse or death (by any cause in the absence of relapse) as assessed by investigator at local site.

TI is defined as no RBC and no platelet transfusion during any consecutive period of at least 56 days post-baseline after starting treatment with AZD3632 or cessation of treatment with AZD3632 but prior to start of subsequent new therapy.

EFS for participants with acute leukaemia is defined as the time from date of first dose until date of relapse, progressive disease, failure to achieve at least Morphologic leukaemia-free state (MLFS) by end of Cycle 6, or death due to any cause as assessed by investigator at a local site. EFS for participants with MDS is defined as the time from date of first dose until date of relapse, progressive disease, failure to achieve at least HI by end of Cycle 6, or death due to any cause.

OS is defined as the time from date of first dose until date of death due to any cause regardless of whether the participant withdraws from study therapy or receives another anticancer therapy.

Percentage of participants with acute leukaemia and MDS who receive subsequent allogeneic HSCT will be reported.

ORR in participants with myelodysplastic syndromes (MDS) is defined as the percentage of participants who have a CR (or CR equivalent), CRL, CRh, PR, or HI as determined by investigator at a local site.

Time to progression to AML is defined from the time of first dose of AZD3632 until first diagnosis of AML, regardless of discontinuation of treatment or receiving of subsequent therapy.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 13 locations
Suspended
Research SiteDecatur, United StatesSee the location
Suspended
Research SitePortland, United States
Suspended
Research SiteHouston, United States
Suspended
Research SiteToronto, Canada
Recruiting soon13 Study Centers