A study testing AZD3632 alone or with other anticancer drugs in adults with acute leukemia or myelodysplastic syndromes with HOX gene overexpression

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What is this study about?

This study involves adults with certain types of blood cancers that have come back or did not respond to previous treatments. The blood cancers being studied include acute leukemia and myelodysplastic syndromes, which are conditions where the bone marrow does not produce healthy blood cells properly. These particular cancers have specific genetic changes that cause overactivity of certain genes called HOX genes. The genetic changes include mutations such as NPM1 mutation, KMT2Ar rearrangements, and several other genetic alterations. The treatment being tested is a medication called AZD3632, which is given as a tablet by mouth. In one part of the study, AZD3632 is given alone, and in another part, it is given together with posaconazole, which is another medication.

The purpose of this study is to learn how safe AZD3632 is, how well the body tolerates it, how it moves through the body over time, and whether it might help treat these blood cancers. The study is divided into different modules or parts. The first module tests AZD3632 by itself to find the best dose that is both safe and effective. This module also includes a smaller part that looks at whether eating food affects how the body absorbs the medication. The second module tests AZD3632 when given together with posaconazole to see if this combination is safe and to understand how the two medications interact in the body.

During the study, participants will take the study medication and visit the clinic regularly for check-ups. These visits will include physical examinations, blood tests to check how the body is functioning, heart monitoring tests, and assessments to see how the disease is responding to treatment. The doctors will monitor for any side effects and measure various aspects of how the medication works in the body, including the levels of medication in the blood at different times. For participants with acute leukemia, the doctors will look for signs that the cancer is responding, such as a reduction in cancer cells in the bone marrow and blood. For those with myelodysplastic syndromes, the doctors will check whether blood cell counts improve and whether participants need fewer blood transfusions. The study will also track how long any positive responses last and overall survival.

1 Initial treatment period

Your treatment will begin with AZD3632, which is an investigational medication being tested for blood cancers with specific genetic changes. This medication comes as a film-coated tablet that is taken by mouth.

The study is divided into different modules. In Module 1, you will receive AZD3632 alone. In Module 2, you may receive AZD3632 together with another medication called posaconazole.

The exact dose of AZD3632 you receive will be determined during the study. The study team is working to identify the most appropriate dose that provides benefit while being well tolerated.

2 Regular monitoring visits

Throughout the study, you will attend regular visits where various tests and examinations will be performed to monitor your health and how the medication is affecting your body.

These monitoring activities will include blood tests to check your organ function and blood cell counts, physical examinations, measurement of vital signs such as blood pressure and heart rate, and electrocardiograms (heart rhythm tests).

Blood samples will also be collected at specific times to measure the levels of the study medication in your bloodstream. This helps understand how your body processes the medication over time.

3 Food effect assessment (if applicable)

Some participants may be asked to take part in an additional assessment to understand how food affects the medication. This is optional and not all participants will be included in this part.

If you participate in this assessment, you will be asked to fast overnight for at least 10 hours before one dose of the medication. On another occasion, you will be asked to eat a high-fat meal before taking the medication.

Blood samples will be collected after each dose to compare how the medication is absorbed with and without food.

4 Assessment of treatment response

During the study, your disease will be regularly assessed to determine how it is responding to the treatment. This will involve blood tests and possibly bone marrow examinations.

For acute leukemia, the study will evaluate whether you achieve a complete response, which means no detectable cancer cells, or a complete response with partial recovery of blood cell counts.

For myelodysplastic syndrome, the study will assess your overall response, which may include complete response, partial response, or improvement in blood cell counts.

The study will also track how long any response lasts, whether you become independent of blood transfusions, and your overall health outcomes over time.

5 Module 2 combination treatment (if applicable)

If you are enrolled in Module 2, you will receive AZD3632 in combination with posaconazole. Posaconazole is an antifungal medication that is being tested together with AZD3632.

Blood samples will be collected to measure the levels of both medications in your bloodstream and to understand how they interact when given together.

The same monitoring activities described earlier will continue throughout this phase, including safety assessments and disease response evaluations.

6 Ongoing safety monitoring

Throughout your participation, any side effects or health changes you experience will be carefully recorded and assessed. This includes any new symptoms, changes in existing symptoms, or abnormal test results.

The study team will monitor whether any dose adjustments, treatment delays, or discontinuations are needed based on how you tolerate the medication.

All adverse events, whether related to the study medication or not, will be documented as part of the safety evaluation.

7 Optional genetic research

You may be offered the opportunity to participate in optional genetic research as part of the study. This involves providing samples for additional genetic testing.

Participation in this genetic research is entirely voluntary. You can choose not to participate in this part without affecting your participation in the main study.

If you choose to participate, you will be asked to sign a separate consent form specifically for this optional research.

8 Long-term follow-up

The study will continue to follow your health outcomes over an extended period. This includes tracking your overall survival and whether you proceed to receive a stem cell transplant after completing the study treatment.

For participants with myelodysplastic syndrome, the study will also monitor the time until progression to acute leukemia, if this occurs.

The estimated end date for the entire study is December 2028, although your individual participation duration may vary based on how you respond to treatment and your overall health status.

Who Can Join the Study?

You must be at least 18 years old when you sign the consent form (in some locations, 16 years old may be allowed)
You must have a diagnosis of acute leukaemia (a type of blood cancer that develops quickly) or myelodysplastic syndromes (a condition where the bone marrow does not make enough healthy blood cells) according to medical classification standards
Your disease must have specific genetic changes that are linked to increased levels of certain genes called HOX genes, including changes such as NPM1 mutation, KMT2A rearrangements, or other specific genetic alterations that will be tested by your medical team
Your disease must have come back after treatment or not responded to previous treatments, and you must not have any other approved treatment options currently available
Your disease must be measurable, meaning doctors can track it through tests
Your major organs (such as heart, liver, and kidneys) must be working well enough
If you or your partner can have children, you must agree to use birth control methods as required by local regulations during the study
You must be able to understand and sign the consent form, and you must be willing to follow all study requirements and restrictions
For certain parts of the study, you may need to be willing to fast overnight (not eat for at least 10 hours) before eating a high-fat meal as part of the research
You may be asked to provide samples for optional genetic research, but this is not required to participate in the main study

Who Cannot Join the Study?

The study does not list specific exclusion criteria in the provided information, meaning detailed reasons why patients cannot participate are not available in these documents.
Generally, clinical trials have exclusion criteria to ensure patient safety and study accuracy, but these specific details would need to be obtained from the complete study protocol.
Patients interested in this study should discuss their individual medical situation with their doctor to determine if they are suitable candidates.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Technische Universitaet Dresden	Dresden	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany

Other Sites

Site Name	City	Country
Rigshospitalet	Copenhagen	Denmark
Azienda Unita Sanitaria Locale Della Romagna	Faenza	Italy
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
Mbtwtjrsappdygzntelwzhyfmt Hjdvacrckxbmugtd	Halle (Saale)	Germany
Gfiljy Upbxbslqsz Fqrrtuwoh	Frankfurt	Germany
Ktsvgqvc dsg Uoopbfoingfr Mnbwycdl Adk	Munich	Germany
Adkvmrt Usqfy Szkorjukj Ltisij Dp Bdhylhn	Bologna	Italy

Trial status

Country	Status	Recruitment Start
Denmark	Recruiting	01.12.2025
Germany	Recruiting	01.12.2025
Italy	Recruiting	01.12.2025

Trial locations

Investigated drugs:

AZD3632

AZD3632 is an experimental medicine being tested in people with advanced blood cancers. It is designed to work against certain genetic changes in cancer cells that cause high levels of a protein called HOX. In this trial, it will be given either alone or together with other cancer treatments to see if it is safe and how well it works.

Posaconazole is an antifungal medicine that is normally used to prevent or treat fungal infections. In this trial, it will be given together with AZD3632 to see how the two medicines work when taken at the same time and whether this combination is safe.

Investigated diseases:

Relapsed Acute Leukemia – Acute leukemia is a cancer of the blood and bone marrow where abnormal white blood cells multiply rapidly and crowd out healthy blood cells. When the disease is described as relapsed, it means the cancer has returned after a period of improvement following treatment. The abnormal cells build up quickly in the bone marrow and blood, preventing the body from producing enough normal blood cells. This leads to symptoms such as fatigue, frequent infections, easy bruising, and bleeding problems. In cases with HOX overexpression genotypes, certain genes that control cell development are more active than normal, which contributes to the uncontrolled growth of leukemia cells. The disease progresses rapidly without appropriate intervention.

Refractory Acute Leukemia – Refractory acute leukemia is a form of blood cancer where the disease does not respond adequately to initial treatment attempts. The cancerous white blood cells continue to multiply in the bone marrow and bloodstream despite therapy. These abnormal cells interfere with the production of healthy red blood cells, white blood cells, and platelets. Patients experience ongoing symptoms including weakness, increased susceptibility to infections, and abnormal bleeding. In cases with HOX overexpression genotypes, specific genes involved in cell growth are abnormally active, driving the persistence of leukemia cells. The condition remains active and continues to worsen as the malignant cells resist standard treatment approaches.

Myelodysplastic Syndromes – Myelodysplastic syndromes are a group of disorders in which the bone marrow fails to produce enough healthy blood cells. The bone marrow creates blood cells that are abnormally shaped and do not function properly, and these defective cells often die earlier than normal cells. This results in low numbers of one or more types of blood cells in the bloodstream. Patients may experience fatigue, shortness of breath, unusual paleness, frequent infections, and easy bleeding or bruising. In cases with HOX overexpression genotypes, genes that regulate blood cell development are overactive, contributing to the abnormal cell production. The condition can remain stable for some time but may gradually worsen and potentially progress to acute leukemia.

Trial ID:

2025-521299-76-00

Protocol code:

D8620C00001

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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A study testing AZD3632 alone or with other anticancer drugs in adults with acute leukemia or myelodysplastic syndromes with HOX gene overexpression

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?