A study looking at AC220, plerixafor or ganetespib alongside chemotherapy for acute myeloid leukaemia and high risk myelodysplastic syndrome (AML18 Pilot)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Acute leukaemia
Acute myeloid leukaemia (AML)
Blood cancers
Myelodysplastic syndrome (MDS)




Phase 1/2

This is a pilot study to see if it would be possible to look at 3 new treatments alongside chemotherapy in a large trial called AML18. It is for people who are over 60 and have acute myeloid leukaemia or a condition called myelodysplastic syndrome that is considered to be at high risk of changing into leukaemia.

More about this trial

Doctors usually treat acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with chemotherapy. As long as patients are fit enough, they have intensive treatment which aims to get rid of all the leukaemia cells, and stop them coming back. This trial is for people who are having intensive treatment for AML or MDS.

You may have a combination of the chemotherapy drugs daunorubicinAra C and etoposide (also known as DAE). Or you may have a combination of the chemotherapy drugs daunorubicin and clofarabine (DClo).

We know from research that both DAE and DClo work well, but researchers want to find out if one drug combination is better than the other.

In this study, they also want to find out more about 3 drugs called AC220, plerixafor and ganetespib.

AC220 is a drug called a tyrosine kinase inhibitor. Tyrosine kinases are body chemicals that send out signals telling cells to grow and divide. Some leukaemia cells have a change (mutation Open a glossary item) to a gene called FLT3. This causes the cells to make too much tyrosine kinase. Doctors think that AC220 may stop the FLT3 genes making too much tyrosine kinase. And so may help stop the leukaemia cells from growing and dividing.  They are testing different doses of AC220.

All blood cells develop from one type of cell called a stem cell. They grow in your bone marrow, before moving into your bloodstream. Plerixafor blocks a protein on the surface of stem cells that ‘ties’ them to the bone marrow. We know from research that plerixafor can help move stem cells from the bone marrow into the bloodstream. Researchers want to find out if plerixafor also helps to move leukaemia cells into your bloodstream, and if it makes them more sensitive to chemotherapy.

Ganetespib is a type of biological therapy called a heat shock protein 90 inhibitor. It stops signals that cancer cells use to divide and grow.

The aims of this pilot study are to

  • See if it would be possible to combine either AC220, plerixafor or ganetespib with chemotherapy in a large trial
  • Find the highest dose of AC220 you can have alongside chemotherapy
  • See if any of the new treatments help people with AML or MDS
  • Learn more about the side effects

Who can enter

You may be able to enter this trial if you

  • Have acute myeloid leukaemia or myelodysplastic syndrome with 1 in 10 (10%) or more of your blood cells being immature (blasts) and a high risk of the MDS becoming leukaemia – your doctor can advise you about this
  • Are over 60 years of age
  • Have satisfactory blood test results
  • Are willing to use a reliable form of contraception during the trial if there is any chance your partner could become pregnant

You cannot enter this trial if you

As well as the above, you cannot have AC220 or ganetespib if you have had a heart attack in the last year, heart pain (angina) in the last 6 months, or have any other heart condition that is a cause for concern – the trial doctors can advise you about this.

Trial design

This pilot study is looking at 3 different treatments. Your doctor will talk to you about which treatment you can have.

  • People in one group have DAE chemotherapy and AC220
  • People in another group have DClo chemotherapy and plerixafor
  • People in the final group have DAE chemotherapy and ganetespib

Depending on when you join the trial, there may already be enough people in one group, so you would only be able to join one of the others. And if you have any sort of heart problem, you cannot join the groups having AC220 or ganetespib.

If, when you join the study, it is possible that you could have any of the treatments, the trial doctor will discuss this with you and then you can choose which one to have.

People in all groups have 3 cycles of treatment. A cycle consists of a few days of chemotherapy, followed by a rest period of 3 or 4 weeks before starting the next treatment.

You have DAE chemotherapy into a vein for 10 days in the 1st cycle of treatment, 8 days in the 2nd cycle and 5 days in the 3rd cycle.

Some people having DAE chemotherapy also take AC220 tablets. The first few people joining this group take the tablets for 1 week in each treatment cycle. If they don’t have any bad side effects, some of the next people joining the study take them for 2 weeks and if they don’t have any bad side effects, some people will then take them for 3 weeks in each cycle.

Some people having DAE chemotherapy also have ganetespib. Everybody in this group will have the same dose of ganetespib. You have it through a drip into a vein, 3 times in each cycle of treatment. It takes about an hour each time.

If you have DCLo chemotherapy, you have it through a drip into a vein for 5 days in each treatment cycle. People having DClo also have plerixafor on each of the 5 days they have chemotherapy. You have it as an injection just under your skin (a subcutaneous injection) 4 hours before you have the chemotherapy drugs.

The first few people joining this group have plerixafor in the 1st treatment cycle only. The next few people have it in the 1st and 2nd cycles, and people joining the study later have it in all 3 treatment cycles. The last few people joining this group also have injections of a growth factor called G-CSF in the 2nd and 3rd treatment cycles. You have this as an injection under your skin each day for 5 days, starting the day before your chemotherapy.

Hospital visits

You will see the study doctor and have some tests before you start treatment. The tests include

During the treatment, you have regular blood tests and you have a bone marrow test after each cycle of treatment. People having AC220 also have a number of ECGs.

Side effects

The side effects of chemotherapy for AML include

We have more information about other possible side effects of daunorubicin, Ara C, etoposide and clofarabine.

The possible side effects of AC220 include changes to your heart rhythm.

The possible side effects of plerixafor include

  • An increased risk of  bruising or bleeding
  • Weakness
  • Dizziness or feeling as if you might pass out
  • Pain in your upper stomach, spreading to your shoulder or back
  • Feeling or being sick
  • Diarrhoea or constipation
  • Dry mouth or numbness in or around your mouth
  • Upset stomach, bloating or wind
  • Tiredness (fatigue)
  • Trouble sleeping
  • Headache, joint or muscle pain
  • Increased sweating
  • Itching, rash, or other irritation at the injection site

The possible side effects of ganetespib include

  • Diarrhoea
  • Fatigue
  • Feeling or being sick
  • A drop in the number of red blood cells (anaemia Open a glossary item)
  • Loss of appetite
  • Tummy (abdominal) pain

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Alan Burnett

Supported by

Cardiff University
Experimental Cancer Medicine Centre (ECMC)
National Institute for Health Research Cancer Research Network (NCRN)

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 7611

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Cara took part in a clinical trial

A picture of Cara

"I am glad that taking part in a trial might help others on their own cancer journey.”

Last reviewed:

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