A study of lenalidomide for acute myeloid leukaemia or high risk myelodysplastic syndrome in people who have an abnormality in chromosome 5 (Len5)

Please note this trial is no longer recruiting patients.

This study is looking at lenalidomide (Revlimid) on its own and in combination with chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome in people who have changes to a particular chromosome (a ‘chromosomal abnormality’).

The first treatment for acute myeloid leukaemia (AML) is usually chemotherapy. The first phase of treatment is called ‘remission induction’ and aims to get rid of all signs of the leukaemia. But this type of chemotherapy can cause serious side effects. So researchers are looking for treatments that target the leukaemia cells but cause fewer side effects.

Myelodysplastic syndrome (MDS) is a condition affecting the bone marrow. If you have MDS, your bone marrow makes abnormal blood cells, but not enough healthy blood cells. MDS can sometimes develop into leukaemia. If you have a lot of abnormal cells in your bone marrow, there is a higher risk of the MDS becoming leukaemia. You may hear this called high risk MDS. The only treatment that can cure MDS is a stem cell transplant. But some people don’t have a donor and this is an intensive treatment with a lot of side effects.

More than 1 in 10 people (11%) with AML have an abnormality on chromosome 5 – part or all the chromosome is missing. Some people with high risk MDS have this abnormality too.

Lenalidomide is a type of biological therapy. It works mainly by helping the body’s immune system target cancer cells. We know from earlier research that lenalidomide can help people with low risk MDS where chromosome 5 is missing. Researchers think it may help people with high risk MDS or AML who have a chromosome 5 abnormality. The aims of this study are to

See if it is safe to have lenalidomide on its own or with chemotherapy for AML or high risk MDS
Learn more about the side effects
Find out if it helps people with AML or high risk MDS

Recruitment

Start 13/07/2009

End 16/11/2010

Phase

Pilot

Who can enter

You can enter this trial if

You have acute myeloid leukaemia or high risk MDS and have an abnormality on chromosome 5
Your doctors think intensive chemotherapy is a suitable treatment for you
You have satisfactory blood test results
You are well enough to take part in the trial (performance status of 0, 1 or 2 )
You are at least 18 years old
You are willing to use reliable contraception for 4 weeks before starting treatment, during the trial and for 4 weeks afterwards (women) or 1 week afterwards (men), if there is any chance you or your partner could become pregnant

You cannot enter this trial if you

Have had an experimental drug as part of another clinical trial in the last 4 weeks
Have any other cancer
Have already had lenalidomide
Are sensitive or allergic to a sugar found in milk called lactose
Have serious heart problems (your doctor can advise you about this)
Have any other serious medical condition
Are known to be HIV, hepatitis B or hepatitis C positive
Are pregnant or breastfeeding

Trial design

The trial will recruit between 40 and 50 people in the UK. The treatment you have will depend on how many immature white blood cells (blasts) there are in your bone marrow when you join the trial.

If you have MDS with a small number of blasts (less than 5%) in your bone marrow
You start by having lenalidomide on its own in 28 day cycles of treatment. You take tablets once a day for 3 weeks followed by a week with no treatment. At the end of each 4 week period, you have a bone marrow test. The trial doctors look at the results to decide what treatment you have next.

If the test shows you still have less than 5% blasts and your bone marrow has recovered from the treatment, you have another cycle of lenalidomide straight away. The treatment can be delayed for up to 4 weeks if it takes longer for your bone marrow to recover. If your bone marrow is still not producing healthy blood cells after 4 weeks, you will come off the trial and your doctor will talk to you about other treatment options.

If you still have a low number of blasts after 2 courses of lenalidomide, you have a 3rd course of tablets. Then, if you have a donor, you may be able to have an allogeneic stem cell transplant. If you don’t have a donor, you can carry on having lenalidomide for a year. Doctors call this ‘maintenance therapy’.

If your blast count has increased after your first or second cycle of lenalidomide, you have induction chemotherapy with lenalidomide. This is

Cytarabine (ARAC) on days 1 to 10
Daunorubicin on days 1, 3 and 5,
Etoposide on days 1 to 5

This combination is known as ‘ADE’. You also have lenalidomide tablets for 10 days. 21 days after finishing the chemotherapy, you have a bone marrow test. If this shows you have less than 5% blasts, or the number of blasts has reduced by at least half, you have 2 more cycles of chemotherapy and lenalidomide. This is called ‘consolidation’. It is the same combination of drugs (ADE), but you have cytarabine for fewer days (days 1 to 8) in each cycle. After this consolidation chemotherapy, you can have a stem cell transplant if you have a donor. Or you can have lenalidomide maintenance therapy for a year.

If you still have too many blasts after induction chemotherapy, you come off the trial and your doctors will talk to you about other treatment options.

If you have AML or MDS with a higher number of blasts (more than 5%) in your bone marrow
You also start by having a cycle of lenalidomide on its own followed by a bone marrow test.

If the number of blasts has reduced by more than half, but is still more than 5%, you have a 2nd course of lenalidomide tablets. After that, depending on how well your disease responds to treatment, you have induction chemotherapy and lenalidomide. Or you go straight to the consolidation treatment.

If the bone marrow test at the end of the first cycle of lenalidomide shows you now have less than 5% blasts and your bone marrow has recovered, you have ADE induction chemotherapy and lenalidomide. The treatment can be delayed for up to a month if your bone marrow has not recovered from the treatment.

At the end of induction chemotherapy, if you have less than 5% blasts or the number dropped by at least half, you will go on to have consolidation treatment, as above. If not, you come off the trial and your doctors will talk to you about other treatments. After the consolidation treatment, you may have a stem cell transplant or maintenance lenalidomide.

Lenalidomide can cause birth defects in the child if it is taken during pregnancy. So, women taking part have a pregnancy test every 4 weeks during the trial, and 4 weeks after finishing treatment.

Hospital visits

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

Physical examination
Blood tests
Heart trace (ECG)
Heart scan (Echocardiogram)
Bone marrow test
Urine test
Pregnancy test (for women who could become pregnant)

When you have lenalidomide on its own, you have blood tests once a week and a bone marrow test at the end of each 4 week treatment cycle.

When you have chemotherapy and lenalidomide, you have to stay in hospital for some time. If you have lenalidomide maintenance therapy, you go to hospital once a month. If you have a stem cell transplant, you will be in hospital for a few weeks at least.

Side effects

The side effects of lenalidomide include

A drop in the number of blood cells that causes an increased risk of infection, tiredness, shortness of breath, bruising and bleeding problems
Tiredness (fatigue)
Rash or dry, itchy skin
Diarrhoea or constipation
Sickness
Taste changes or loss of appetite
Dry mouth
Aching muscles or joints
Fever
Dizziness
Problems sleeping
Swollen arms or legs
Headache
Shaking
Pain, weakness, tingling or change of feeling usually in the hands or feet