A trial of AZD1152 and low dose cytosine arabinoside (LDAC) for acute myeloid leukaemia in older people (The SPARK study)

Who can enter

You can enter this trial if you

• Have been diagnosed with acute myeloid leukaemia and are over 60 years old
• Are not fit enough to have intensive induction treatment
• Have satisfactory blood test results

You cannot enter this trial if you

• Have AML that has spread to your brain or spinal cord unless it has not caused any symptoms for at least 10 days
• Have a type of AML called acute promyeloctic leukaemia or type M3
• Have chronic myeloid leukaemia that is in blast crisis
• Have had another experimental drug as part of a clinical trial in the last 2 weeks, or earlier if you have not recovered from side effects
• Have not recovered from the side effects of other cancer treatment, unless they are very mild
• Have had chemotherapy in the last 2 weeks apart from a drug called hydroxyurea
• Have had radiotherapy in the last 2 weeks apart from radiotherapy for symptoms
• Have had surgery with a general anaesthetic in the last 4 weeks
• Have heart problems that are a cause for concern (the trial doctors can advise you about this)
• Have any other serious medical condition that cannot be controlled with medication
• Are known to be sensitive to anything in AZD1152 or cytosine arabinoside
• Are known to be HIV, hepatitis B or hepatitis C positive
• Are pregnant or breastfeeding

Trial design

This study is in 2 parts. The first part is comparing low dose cytosine arabinoside (LDAC) with AZD1152. After 75 people have been recruited, the second part will go on to look at having both drugs together, to see if this helps people more than LDAC alone.

It is a randomised study. The people taking part are put into treatment groups by a computer. Neither you nor your doctor can decide which group you are in.

In the first part of the study, 2 out of every 3 people recruited have AZD1152. And 1 out of every 3 people recruited have low dose cytosine arabinoside (LDAC).

In the second part, 1 out of 3 of the people have AZD1152, 1 out of 3 have LDAC, and the remaining 1 out of 3 have both drugs at the same time.

You have treatment in 4 week periods known as cycles of treatment. You are expected to have at least 3 cycles of treatment, lasting 12 weeks in total. If treatment is helping, you may carry on having it for longer.

You have AZD1152 through a drip into a vein continuously, via a small portable pump, over 7 days. Then you have 3 weeks without treatment.

You have LDAC as an injection under the skin (subcutaneous injection). You have injections twice a day for the first 10 days of each treatment cycle. You then have 2 ½ weeks with no treatment.

In you join the second part of the study, and are in the group having both drugs, you start them both on the same day.

The study team will ask you to fill out a questionnaire before you start treatment, during each treatment cycle and at the end of treatment. The questionnaire will ask about any side effects you have had and about how you have been feeling. This is called a quality of life study.

When you have treatment for leukaemia, you have a number of bone marrow tests. As part of this study, researchers will use a sample of your bone marrow to study your DNA. This is to learn more about how genes affect the development of leukaemia and the way people respond to treatment. And they will ask for a sample of saliva they can use to study your DNA.

The study team will also ask your permission to take 1 extra blood sample. They will use this, along with some of your bone marrow sample to look for biomarkers. These are substances they can measure, to tell them how a disease is developing or how a treatment is working.

Hospital visits

You will see the trial doctors and have some tests before you start treatment. The tests include

• Physical examination
• Heart trace (ECG)
• Blood and urine tests
• Bone marrow test

You usually stay in hospital during your first cycle of treatment. This is a week if you have AZD1152. It is 10 days if you have LDAC or a combination of both drugs. It may be possible for some people to have the first cycle of treatment as an outpatient. And from the 2nd treatment cycle onwards, more people may be able to have treatment at home. But in the UK, people having AZD1152 usually have to be in hospital for all cycles of treatment.

You see the study doctors regularly during treatment. You have a number of blood tests throughout the study and a bone marrow test towards the end of each treatment cycle.

When you finish treatment, you go back and see the study doctors 4 weeks later. After this, they may ask you to carry on having follow up appointments once a month. Or, they may just ask you to complete a questionnaire.

Side effects

As AZD1152 is a new drug, there may be some side effects we don’t know about yet. The possible side effects that researchers already know about include

• A drop in the number of blood cells causing an increased risk of infection, tiredness, shortness of breath, bruising and bleeding problems
• Hair loss
• Sore mouth
• Dizziness
• Diarrhoea or constipation
• Feeling or being sick
• Tiredness (fatigue)

The possible side effects of LDAC are the same as those listed for AZD1152, but can also include

• Skin rash
• Muscle or bone pain

It is likely that AZD1152 could lead to a loss of fertility and damage to unborn children. Male patients with partners who are pregnant or who could become pregnant should use condoms to avoid pregnancy and to avoid the risk of transferring AZD1152 to their partner. Female patients must be past the menopause.