Acute Lymphoblastic LeukaemiaPhase 1/2MOMENTUMNCT07155226
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
A Phase 1/2 study testing AZD3632 and Posaconazole in people with Acute Lymphoblastic Leukaemia and Acute Myeloid Leukaemia, run by AstraZeneca at 30 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukaemia, Acute Myeloid Leukaemia, Higher-risk Myelodysplastic Syndromes
- What is being tested?
- AZD3632 and Posaconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 30 sitesin 9 countries
- Study dates
- 9 Jan 2026to 15 Feb 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 12Show fewer
- 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.
Trial locations and contacts
30 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
30 sites in 9 countries
United States6 sites, 5 recruiting
- Not yet recruiting
Research Site
Chapel Hill, North Carolina, 27599
- Recruiting
Research Site
Decatur, Illinois, 62526
- Recruiting
Research Site
Durham, North Carolina, 27705
- Recruiting
Research Site
Houston, Texas, 77030
- Not yet recruiting
Research Site
New York, New York, 10065
- Suspended
Research Site
Portland, Oregon, 97239
Germany6 sites, 6 recruiting
- Recruiting
Research Site
Dresden, 01307
- Recruiting
Research Site
Frankfurt A. Main, 60590
- Recruiting
Research Site
Halle, 06097
- Recruiting
Research Site
Heidelberg, 69120
- Recruiting
Research Site
München, 81377
- Recruiting
Research Site
Ulm, 89081
United Kingdom5 sites, 4 recruiting
- Recruiting
Research Site
Edinburgh, EH4 2XU
- Not yet recruiting
Research Site
London, EC1A 7BE
- Recruiting
Research Site
London, SE5 9RS
- Recruiting
Research Site
Manchester, M20 4BX
- Suspended
Research Site
Newcastle, NE7 7DN
Japan3 sites, 3 recruiting
- Recruiting
Research Site
Bunkyō City, 113-8677
- Not yet recruiting
Research Site
Kashiwa, 277-8577
- Recruiting
Research Site
Okayama, 700-8558
South Korea3 sites, 3 recruiting
- Recruiting
Research Site
Seoul, 06351
- Recruiting
Research Site
Seoul, 06591
- Recruiting
Research Site
Seoul, 110-744
Australia2 sites
- Suspended
Research Site
Fitzroy, 3065
- Suspended
Research Site
Perth, WA 6000
Canada2 sites
- Suspended
Research Site
Montreal, Quebec, H3T 1E2
- Suspended
Research Site
Toronto, Ontario, M5G 2M9
Italy2 sites, 2 recruiting
- Recruiting
Research Site
Bologna, 40138
- Recruiting
Research Site
Ravenna, 48121
About this study
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
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.
Read the 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.
- Conditions
- Acute Lymphoblastic Leukaemia, Acute Myeloid Leukaemia, Higher-risk Myelodysplastic Syndromes
- Being tested
- AZD3632, Posaconazole
- Keywords
- Myelodysplastic Syndromes, Menin inhibitor, Anti-leukaemic activity, Anti-fungal agent, HOX overexpression.
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD3632Drug
AZD3632 will be administered orally.
PosaconazoleDrug
Posaconazole will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Module 1: AZD3632 dose 1 | Experimental | Participants will receive AZD3632 (dose 1) through the treatment period. Receives: Drug: AZD3632 |
| Module 1: AZD3632 dose 2 | Experimental | Participants will receive AZD3632 (dose 2) through the treatment period. Receives: Drug: AZD3632 |
| Module 1: AZD3632 dose 3 | Experimental | Participants will receive AZD3632 (dose 3) through the treatment period. Receives: Drug: AZD3632 |
| Module 1: AZD3632 dose 4 | Experimental | Participants will receive AZD3632 (dose 4) through the treatment period. Receives: Drug: AZD3632 |
| Module 1: AZD3632 dose 5 | Experimental | Participants will receive AZD3632 (dose 5) through the treatment period. Receives: Drug: AZD3632 |
| Module 1: AZD3632 dose 6 | Experimental | Participants will receive AZD3632 (dose 6) through the treatment period. Receives: Drug: AZD3632 |
| Module 2: AZD3632 + posaconazole | Experimental | Participants will receive AZD3632 alone, then will receive AZD3632 in combination with posaconazole through treatment period. Receives: Drug: AZD3632; Drug: Posaconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Module 1: Number of participants with dose-limiting toxicity (DLT)
Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.
Measured: 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)
Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.
Measured: 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)
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.
Measured: Up to 30 days after last dose (approximately 3 years 1 month)
Secondary outcomes (29)
Module 1 and Module 2: Maximum concentration (Cmax) of AZD3632
The PK of AZD3632 as monotherapy (module 1) and in combination with posaconazole (module 2) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1 and Module 2: Time of maximum concentration (Tmax) of AZD3632
The PK of AZD3632 as monotherapy (module 1) and in combination with posaconazole (module 2) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Trough concentration (Ctrough) of AZD3632
The PK of AZD3632 as monotherapy will be assessed.
Measured: 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
The PK of AZD3632 as monotherapy will be assessed.
Measured: 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
The PK of AZD3632 as monotherapy (module 1) and in combination with posaconazole (module 2) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Area under concentration-time curve in the dosing interval (AUCtau) of AZD3632
The PK of AZD3632 as monotherapy will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Apparent total body clearance (CL/F) of AZD3632
The PK of AZD3632 as monotherapy will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Apparent volume of distribution based on the terminal phase (VZ/F) of AZD3632
The PK of AZD3632 as monotherapy will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Half-life (t1/2) of AZD3632
The PK of AZD3632 as monotherapy will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Maximum concentration (Cmax) of AZD3632 (food effect)
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Time of maximum concentration (Tmax) of AZD3632 (food effect)
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: 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)
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Area under concentration-time curve in the dosing interval (AUCtau) of AZD3632 (food effect)
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Minimum concentration (Cmin) of AZD3632 (food effect)
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Ratio of Cmax between fed and fasted state
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Ratio of AUC(0-t) between fed and fasted state
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1: Ratio of AUCtau between fed and fasted state
The preliminary effect of food on plasma PK of AZD3632 (conducted in a nested evaluation during backfills) will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 2: Plasma geometric mean ratio of Cmax
The PK pf AZD3632 when co-administered with posaconazole will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 2: Plasma geometric mean ratio of AUC
The PK pf AZD3632 when co-administered with posaconazole will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 2: Plasma concentration of posaconazole
The PK pf AZD3632 when co-administered with posaconazole will be assessed.
Measured: From Day 1 to 3 years 1 month
Module 1 and Module 2: Complete response rate (CR + CRh)
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.
Measured: Up to 3 years 1 month
Module 1 and Module 2: Time to response (TTR)
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.
Measured: Up to 3 years 1 month
Module 1 and Module 2: Duration of response (DoR)
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.
Measured: Up to 3 years 1 month
Module 1 and Module 2: Transfusion Independence (TI)
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.
Measured: Up to 3 years 1 month
Module 1 and Module 2: Event-free Survival (EFS)
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.
Measured: From Cycle 2 Day 1 (each cycle is 28 days) up to disease follow-up (approximately 3 years 1 month)
Module 1 and Module 2: Overall Survival (OS)
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.
Measured: From Cycle 2 Day 1 (each cycle is 28 days) up to disease follow-up (approximately 3 years 1 month)
Module 1 and Module 2: Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)
Percentage of participants with acute leukaemia and MDS who receive subsequent allogeneic HSCT will be reported.
Measured: Up to 3 years 1 month
Module 1 and Module 2: Overall Response Rate (ORR)
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.
Measured: Up to 3 years 1 month
Module 1 and Module 2: Time to Progression to acute myeloid leukaemia (AML)
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.
Measured: Up to 3 years 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2025
- Study start9 Jan 2026
- Primary completion15 Feb 2029 (estimated)
- Study completion15 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukaemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07155226
- Sponsor's protocol ID
- D8620C00001
- Other IDs
- 2025-521299-76-00, 2025
- Acronym
- MOMENTUM
- Status last verified
- Oct 2026
- First submitted
- 14 Aug 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portalVivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.