A trial looking at idasanutlin and cytarabine for acute myeloid leukaemia
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This trial is for people whose acute myeloid leukaemia (AML) has come back or continued to grow following their first or second treatment.
More about this trial
Chemotherapy is the main treatment for acute myeloid leukaemia (AML). Cytarabine is one of the chemotherapy drugs used.
Cancer cells can switch off an important protein. This protein would normally signal that a faulty cell, such as a cancer cell, should die. When the protein is switched off, the cancer cells continue to multiply.
Idasanutlin is designed to switch this protein back on which means the cancer cells will stop growing and die.
Everyone in this trial has treatment with cytarabine. Some people also have treatment with idasanutlin and some have a dummy tablet (placebo).
The aims of this trial are to:
- find out if idasanutlin and cytarabine work better than cytarabine alone
- learn more about the side effects
Who can enter
The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.
You may be able to join this trial if all of the following apply. You
- Have AML that has come back (relapsed) for a first or second time or has continued to grow following 1 or 2 courses of treatment
- Have had no more that 2 induction treatments. One of these must have included treatment with cytarabine and an anthracycline drug, or anthracenedione such as mitoxantrone
- Have satisfactory blood test results
- Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- Are willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance that you or your partner could become pregnant
- Are willing and able to have blood products
- Are at least 18 years old
You cannot join this trial if any of these apply.
Cancer related
- You are younger than 60 years of age (including age 60), you had a complete remission for over 1 year following your first treatment and your AML has now come back (relapsed)
- You have extramedullary AML
- Your AML has affected your brain or spinal cord (CNS) and it is causing symptoms
- Your AML has continued to grow (refractory) or come back (relapsed) within 3 months of treatment with a total dose of over 18g/m2 of cytarabine
- You have had a transplant using stem cells from a donor (an allogeneic transplant) within 3 months of joining this trial
- You have had treatment to suppress your immune system for graft versus host disease in the last 2 weeks
- You have had treatment in a trial in the last month
- Your AML developed because you had previous chemotherapy for another type of cancer
- You have already had treatment with a drug similar to idasanutlin
- You are having any other type of treatment for your AML within 3 months of starting treatment in this trial. You can still take part if you are having hydroxyurea or leukapherisis to keep the levels of white blood cells stable in your blood (although this must be stopped 24 hours before starting treatment in this trial)
- You have any serious side effects from your previous treatment for your AML which are still causing you problems
- You have had any other cancer in the last 5 years unless this cancer has not caused any problems and has not needed treatment in the last 2 years
Medical conditions
- You have another haematological condition such as myelodysplastic syndrome, aplastic anaemia, or myeloproliferative disease
- You are taking drugs that target enzymes in the body called CYP2C8, OATP1B1/3 or CYP3A4 and this treatment can’t be stopped
- You take blood thinning medication such as warfarin or aspirin and this can’t be stopped, you may be able to take part if you are taking low dose heparin
- You have any other medical condition that is severe or uncontrolled. For example, hypertension or diabetes mellitus not properly controlled with medication
- You have had a heart attack or stroke in the last 6 months
- You have a heart condition called QTc prolongation, or a family history of QT syndrome, or you are taking drugs that cause QT prolongation
- You have an infection which needs treatment, or you have recently had treatment for an infection
- You have active or chronic hepatitis unless blood tests show you are clear from infection
- You have significant liver scarring (cirrhosis) with Child-Pugh B and C
- You have problems with very low or very high levels of electrolytes in your blood. Electrolytes include potassium, calcium and magnesium. You might be able to take part if you have treatment to correct this during the time the doctors are doing tests for you to be able to take part in the trial
- You have HIV
Other
- You are allergic to the drugs used in this trial
- You are pregnant or breastfeeding
Trial design
This is a phase 3 trial. The researchers need 36 people in the UK to join.
It is a randomised trial. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither of you will know which group you are in. This is called a double blind trial.
• One group has cytarabine and idasanutlin
• The other group has cytarabine and a dummy tablet (placebo)
Twice as many people are in the cytarabine and idasanutlin group.
You have idasanutlin or a dummy tablet twice a day. You have a tablet in the morning. Then your second tablet in the evening, about 10 to 14 hours later.
You have cytarabine through a drip into a vein after your morning tablet. This takes between 1 to 3 hours.
You have your tablets twice a day and cytarabine once a day for 5 days. Then you have no treatment for the next 23 days. These are called rest days.
Each period of 28 days (or 3 weeks) is one cycle of treatment.
Your first cycle of treatment aims to get rid of all the leukaemia cells. This is the induction cycle.
Your cancer is in remission if tests show there are no leukaemia cells. You then have 1 or 2 further cycles to stop the AML coming back. These are called consolidation cycles. For consolidation cycles, you have idasanutlin or a dummy tablet once a day (instead of twice a day).
Your doctor might recommend you have a second induction cycle if the treatment has shown some signs of working. But you are not completely in remission.
Your doctor will discuss other treatment options with you if your AML has not responded to induction treatment.
Blood and tissue samples
You have extra blood tests as part of this trial. Where possible these are done at the same time as your routine blood samples. The researchers would also like to collect a sample of your bone marrow whenever this is tested as part of your routine care. For example, when you have a bone marrow aspirate to check for AML.
These blood and bone marrow samples are used to find out what happens to the treatment in your body (pharmacokinetics). And to look for substances called biomarkers to find out why treatment might work for some people and not for others.
The researchers will use some of the samples for genetic research. They want to find more about the role of genes in AML.
Quality of Life
The trial team ask you to fill out a questionnaire before you start treatment and every week while you have treatment. Then every 3 months after you have finished treatment in this trial. The questionnaires ask about side effects and how you are feeling. It looks at your quality of life.
Hospital visits
You see the doctors and have some tests before you start treatment. The tests include:
- blood tests
- physical examination
- heart trace (ECG)
- chest x-ray or CT scan of your chest
- urine test
- bone marrow aspirate to assess your leukaemia and for research purposes
You see a doctor and have blood tests every week during treatment. You have a bone marrow test after each cycle of treatment.
About 4 weeks after your finish treatment you see the doctor again and have some of the same tests as above. You then see a trial doctor every 3 months. They will ask about side effects and about any further treatment you might have had.
If your leukaemia comes back, the researcher would like a sample of any bone marrow tests you have.
Side effects
As idasanutlin is a new drug, there may be side effects we don’t know about yet. Possible side effects include:
- diarrhoea
- feeling or being sick
- loss of appetite
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Cytarabine can cause cytarabine syndrome in the first 24 hours following your treatment. Symptoms include:
- flu like symptoms
- raised temperature
- aching muscles and bones
- skin rash
- sore pink eyes
- chest pain – contact your doctor straight away if you have chest pain
Your doctor or nurse will give you a contact number to ring if you have any concerns or questions.
Common side effects of cytarabine also include:
- loss of appetite
- feeling or being sick
- tummy pain
- sore mouth
- sore, inflamed anus –ask your doctor about creams that might help to relieve this
Blood tests results might show changes to the way your liver works These liver changes are usually mild and tend not to cause symptoms. These usually go back to normal when treatment is finished. You have regular blood tests to monitor this
We have more information about cytarabine.
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.
Chief Investigator
Dr Steve Knapper
Supported by
Roche
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
