Ask to take part

Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.

Contact Information:

Dr Lucy Marsh
-
Optimise-FLT3@cardiff.ac.uk


Dr Steven Knapper
+44 (0)292 074 7747
knappers@cardiff.ac.uk


Study Location:

Find another location


Questions to ask
Skip to Main Content
English | Cymraeg
Be Part of Research - Trial Details - Optimising therapy in FLT3-mutated acute myeloid leukaemia
Back

Optimising therapy in FLT3-mutated acute myeloid leukaemia

Recruiting

Open to: All Genders

Age: Mixed

$location.addressLine3

Medical Conditions

Acute myeloid leukemia

This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.


Acute myeloid leukaemia is an aggressive blood cancer and is the most common form of acute leukaemia in adults, the majority of who will die from the disease. Younger and fitter patients can have treatment aiming to cure the disease with cycles of intensive chemotherapy followed for some patients by stem cell transplant. Survival rates have gradually increased following improvements to chemotherapy, transplantation, better general care measures and new targeted drugs for patients in specific AML sub-groups. This study focuses on a subgroup of AML with mutations in the FLT3 gene, found in about one-third of AML patients. These patients have worse overall outcomes due to increased rates of early disease relapse. Clinical trials have recently identified several promising strategies to improve outcomes for patients with FLT3 AML but these approaches have not yet been combined in a single trial. Currently the standard treatment is standard intensity DA chemotherapy combined with midostaurin. We will compare this standard treatment with two new combinations. One is standard-intensity chemotherapy combined with both midostaurin and GO; this combination has already undergone pilot testing in the AML19 study and was safe and appeared very effective. The second new combination is intensified chemotherapy (FLAG-Ida) combined with midostaurin and GO. Pilot safety testing of this combination is built into this study.

Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.  

The recruitment start and end dates are as follows:

01 Feb 2025 31 Jan 2031

Participants will be randomly allocated to one of the three treatment schedules. They will receive up to four cycles of intensive chemotherapy treatment, including stem cell transplant in selected cases; during this time the response of the leukaemia to treatment will be measured by blood and bone marrow tests to see whether patient outcomes are improved in terms of increased survival, reduction in rates of relapse and reduction in the need for stem cell transplant and the researchers will monitor for any increased side effects associated with the intensified treatment schedules.


Patients aged 16 years and over with AML

You can take part if:



You may not be able to take part if:


1. Receipt of any previous therapy for AML or any antecedent haematological condition (the use of oral hydroxycarbamide to control white blood cell count is permitted)2. Other active malignancy requiring treatment3. Patients who are pregnant or lactating4. Uncontrolled infection with Human Immunodeficiency Virus (HIV) or Hepatitis B or C. Patients with known chronic infections who are receiving or have completed therapy and have recent documented negative viral PCR tests are not excluded5. Blast transformation of chronic myeloid leukaemia (CML)


Below are the locations for where you can take part in the trial. Please note that not all sites may be open.

  • -
    -

Because you might get randomised to the “standard care” arm, and because we don’t yet know whether the “test arms” are any better, there is no certainty that you will benefit directly from taking part in the trial, however, this is possible. The information from the trial results will help to improve the treatments for future patients with FLT3-mutated AML.
AML chemotherapy causes side effects and carries a risk of infection or bleeding because it damages normal blood cells as well as leukaemia cells. The usual effects of chemotherapy include hair loss, sore mouth, some nausea and sometimes vomiting although these are usually controlled with medication, damage to the immune system and problems with fertility. After each course of chemotherapy patients will be reviewed regularly by medical teams and all side effects are reported to the trial.
Midostaurin is a licenced treatment when given with DA chemotherapy, but in the “test arms” it is being used with different or additional chemotherapy drugs. The team will monitor data from the trial very closely to minimise any risk to participants. Common side effects of Midostaurin include nausea and stomach upset.
Mylotarg is licenced to treat AML in combination with DA chemotherapy. Chemotherapy will cause hair loss, sore mouth and, suppress the immune system but Mylotarg does not seem to make this worse. Liver function is a concern for patients receiving Mylotarg, therefore liver function-based eligibility criteria apply at the point of study entry and liver function test-based stipulations are applied as go/no-go before each Mylotarg dose.
FLAG-Ida (Fludarabine, Ara-C, G-CSF & Idarubicin) is a combination of three chemotherapy drugs and one “growth factor” (G-CSF) that has been used to treat AML for many years. It is more intensive than standard DA chemotherapy and may be associated with longer suppression of bone marrow following each cycle.
The combinations of drugs in experimental arms may have potential side effects and there may be risks involved in combining treatments in the experimental arms that have not yet been tested, therefore, the trial team will monitor data from the trial very closely to minimise any risk to participants. Some patients may need to delay doses of chemotherapy to allow the side effects to get better.
Experimental arm 2: Most of the possible side effects listed in the PIS are mild to moderate. However, some side effects can be very serious and life-threatening and may even result in death. It is possible that the patient's cancer may not improve during the study or may even worsen. Some side effects do not need treatment, while others generally get better with treatment. Safety data will be collected for experimental arm 2 and will be reviewed. The PIS details the full side effects of treatments and assures the patients that their doctor will be able to explain more details about the chemotherapy that they will receive and how it will be given.
The later part of AML19 included a 77-patient single-arm pilot of the combination DA-GO-Mido (termed ‘Midotarg’) to investigate the safety and preliminary efficacy of combining intensive chemotherapy with both midostaurin and GO. The combination was well tolerated, with no 60-day mortality, no excess toxicity and an encouraging overall response rate.
Experimental arm 3: Most of the possible side effects listed in the PIS are mild to moderate. However, some side effects can be very serious and life-threatening and may even result in death. It is possible that the patient's cancer may not improve during the study or may even worsen. There may be risks involved in taking the new combination of these drugs that have not yet been discovered. There is always a risk involved in taking an experimental drug, but every precaution will be taken, and patients will be closely looked after by the doctors and research nurses. If a patient suffers any side effects or injuries, or their condition gets worse, they are advised to tell their doctor/nurse immediately so that they can receive appropriate care.
The FLAG-Ida-GO-Mido schedule has not yet been piloted, therefore this arm includes a safety run-in phase where the first 20 patients will undergo enhanced pharmacovigilance. Safety data will be collected on a weekly basis following the commencement of FLAG-Ida-GO-Midostaurin. The IDMC will review safety data after 10 and 20 patients have been treated. They will particularly focus on increased haematological toxicity (delayed count recovery following courses 1 and 2), infective complications and evidence of increased 60-day mortality.
If these or other concerning toxicities are observed, the study team will act in close liaison with the IDMC. Contingencies to modify the arm 3 treatment schedule will depend on when toxicity is observed (post course 1 vs course 2) and whether it is age group-related (younger vs older patients)
Risks associated with general trial procedures:
Blood samples: Taking blood may result in pain, irritation, bruising, bleeding, and irritation at the injection site. There is also a possibility of fainting or infection
Bone marrow samples: There is a risk of pain, bleeding, problems with wound healing, bruising and/or infection
Completing QoL questionnaires: May be considered upsetting by the participants but will be completed with support from staff

Dr Steven Knapper
+44 (0)292 074 7747
knappers@cardiff.ac.uk


Dr Lucy Marsh
-
Optimise-FLT3@cardiff.ac.uk



The study is sponsored by Cardiff University and funded by Cancer Research UK.



We'd like your feedback

Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.


Is this study information helpful?

What will you do next?
Read full details for Trial ID: ISRCTN34016918

Or CPMS 57535

Last updated 16 May 2025

This page is to help you find out about a research study and if you may be able to take part

You can print or share the study information with your GP/healthcare provider or contact the research team directly.   

Back to the top