RecruitingPhase II/IIIInterventional

Optimising therapy in FLT3-mutated acute myeloid leukaemia

Acute myeloid leukaemia (AML) is an aggressive blood cancer. About one in three people with AML have a change in a gene called FLT3. This mutation can make the leukaemia grow faster and makes it more likely to return after treatment. Currently, the standard NHS treatment for fit patients combines regular chemotherapy with a targeted drug called midostaurin. This UK trial, funded by Cancer Research UK, compares that standard approach against two new combinations. Both new approaches add another targeted medicine called gemtuzumab ozogamicin (Mylotarg), either with standard chemotherapy or a stronger chemotherapy mix known as FLAG-Ida. The goal is to see if these new combinations help people live longer, lower the chance of the leukaemia coming back, and reduce the need for stem cell transplants, while keeping side effects manageable. Participants receive up to four cycles of hospital-based chemotherapy.

At a glance

Status

Recruiting

Phase

Phase II/III

Sponsor

Cardiff University

Enrolment target

390

Start

01 Feb 2025

Estimated completion

31 Dec 2030

Acute myeloid leukemia

What is this study about?

Acute myeloid leukaemia (AML) is a fast-growing cancer of the blood and bone marrow. In around a third of patients, the leukaemia cells carry a specific fault in a gene known as FLT3. This genetic change acts like an 'on switch', causing leukaemia cells to multiply quickly. Patients with this gene change face a higher risk of their cancer returning after standard treatment, which is why researchers are urgently searching for better options.

Currently, standard care involves intensive chemotherapy combined with a targeted drug called midostaurin, which specifically blocks the faulty FLT3 protein. While this has improved outcomes, doctors want to see if adding another targeted medicine, gemtuzumab ozogamicin (also called Mylotarg), can clear the cancer cells even more effectively. Mylotarg works like a guided missile, delivering chemotherapy directly to leukaemia cells.

The OPTIMISE-FLT3 trial tests three different treatment paths. One group receives the current standard care. A second group receives standard chemotherapy combined with both midostaurin and Mylotarg. A third group receives a stronger chemotherapy mix called FLAG-Ida, alongside both targeted medicines.

By comparing these three approaches, doctors hope to learn which combination gives the highest chance of long-term recovery, reduces disease relapse, and helps patients avoid the need for intensive bone marrow transplants.

Key takeaways

Tests new drug combinations for people with FLT3-mutated acute myeloid leukaemia (AML).
Compares standard chemotherapy against two newer combinations using targeted drugs.
Open to people aged 16 and over who are fit enough for intensive hospital chemotherapy.
Aims to improve survival, reduce cancer relapse, and lower the need for stem cell transplants.
Involves up to four cycles of intensive treatment in hospital followed by regular check-ups.

Who may be eligible?

This trial is open to people aged 16 and over who have been diagnosed with acute myeloid leukaemia (AML). Because the treatments tested are intensive, participants must be physically fit enough to handle strong chemotherapy, as assessed by their hospital doctor.

In most cases, participants need to have the FLT3 gene change confirmed by laboratory tests. However, because AML can progress very quickly, doctors can start patients on the trial immediately if urgent treatment is required while waiting for the genetic test results.

To join, your kidneys and liver must be functioning reasonably well, which will be checked using routine blood tests. Pregnant women cannot take part, and both men and women must agree to use reliable contraception during treatment and for six months afterwards.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 16 or older.
I have been diagnosed with acute myeloid leukaemia (AML).
My doctor considers me fit enough for intensive chemotherapy.
I have a confirmed FLT3 gene change, or need urgent treatment while testing is underway.
I do not have severe kidney or liver problems.
I am not pregnant and agree to use effective contraception if needed.

Answer every question to see your result.

What does participation involve?

If you join this study, a computer will randomly assign you to one of the three treatment groups. You will receive up to four cycles of intensive chemotherapy. Because this treatment temporarily weakens your immune system, each cycle involves staying in hospital for several weeks to receive your medicines through a drip and take capsules by mouth. Some patients may also have a stem cell transplant if their care team decides it is the best next step.

During your stay and afterwards, you will have regular blood tests, physical examinations, and bone marrow biopsies to check how well the leukaemia is responding. You will also be asked to fill in short questionnaires about how you are feeling. After finishing your treatment cycles, your medical team will follow up on your health regularly for several years. The overall trial is scheduled to run until late 2030.

Potential risks and benefits

Taking part could mean you receive a treatment that works better than standard care, but this cannot be guaranteed because the combinations are still being tested. The information gathered will help doctors treat future AML patients more effectively. Intensive leukaemia treatment carries significant risks, including tiredness, hair loss, mouth ulcers, sickness, and temporary damage to fertility. Chemotherapy lowers your healthy blood cells, putting you at high risk of infections and bleeding that require prompt hospital care. The trial drugs can also affect liver function or cause blood counts to recover more slowly. Your safety is monitored closely throughout, and you are free to leave the trial at any time without it affecting your standard medical care.

Locations (47)

The Christie
Approximate
Manchester, England
Clatterbridge Cancer Centre -wirral
Approximate
Wirral, England
Maidstone Hospital
Approximate
Maidstone, England
University Hospital
Approximate
Nottingham, England
Royal Bournemouth Hospital
Approximate
Bournemouth, England
Royal Cornwall Hospital
Unverified
Truro, England
Royal Derby Hospital
Unverified
Derby, England
Torbay Hospital
Unverified
Torquay, England
Guys Hospital
Unverified
London, England
Glan Clwd Hospital
Unverified
Rhyl, England
Queen Alexandra Hospital
Unverified
Portsmouth, England
Salisbury District Hospital
Unverified
Salisbury, England

Common questions

How is it decided which treatment group I join?

A computer programme chooses your treatment group at random. Neither you nor your doctor can choose the group, ensuring the study results are fair and unbiased.

Will I still be able to have a stem cell transplant?

Yes. If your medical team feels that a stem cell transplant is the safest and most effective option for you after chemotherapy, you can still have one.

Do I have to pay to take part in this trial?

No. The trial is funded by Cancer Research UK and run through the NHS. All trial medications and study tests are provided without charge.

What happens if my tests show I do not have the FLT3 mutation?

If you needed urgent treatment before test results arrived and it turns out you do not have the mutation, your doctors will discuss your results with you and adjust your care plan as needed.

Can I leave the study if I change my mind?

Yes, taking part is completely voluntary. You can withdraw from the trial at any point without giving a reason, and your medical team will continue to give you the best standard care.

How to find out more

Lucy Marsh

Optimise-FLT3@cardiff.ac.uk - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.