A trial looking at selumetinib and dexamethasone for acute lymphoblastic leukaemia (SeluDex)

Cancer type:

Acute leukaemia
Acute lymphoblastic leukaemia (ALL)
Blood cancers
Children's cancers
Leukaemia

Status:

Open

Phase:

Phase 1/2

This trial is looking at combining selumetinib with dexamethasone for children and adults with acute lymphoblastic leukaemia (ALL).

It is open to people with ALL that has come back after treatment (relapsed) or has continued to get worse during treatment (refractory). And the leukaemia has a gene change (mutation Open a glossary item) in the RAS-pathway that controls the MEK protein.

Cancer Research UK supports this trial.

More about this trial

MEK is a protein inside cells that sends signals for them to grow and to stop growing. In some leukaemia cells there is a change in the genes of the cells. This change causes the MEK protein to signal to the leukaemia cells to continue to grow abnormally.

Selumetinib is a targeted cancer drug. It works by blocking the signals from the MEK protein. This might help stop or slow down the growth of the leukaemia cells.

Dexamethasone is already a treatment for leukaemia.

Researchers think that combining selumetinib with dexamethasone might help people with ALL that has come back after treatment or continued get worse during treatment.

In this trial the team want to find the best dose of selumetinib to give with dexamethasone. And then use this dose to find out how well this combination works for people with ALL. They also want to find how safe this combination is and what the side effects are.

Before having treatment in this trial the researchers need to know if your leukaemia has the gene change in the RAS-pathway that controls the MEK protein. They will look at a sample of your bone marrow Open a glossary item to find this out.

In the case your leukaemia doesn’t have the gene change your doctor will talk to you about other treatment options that might be open to you.

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 acute lymphoblastic leukaemia (ALL) that has come back after treatment or got worse during treatment. If you are 18 years or older you must have had at least 1 treatment already, if you are younger than 18 years old you must have had 2 treatments already
  • have ALL that has a gene change in the RAS-pathway, you will have a test for this as part of the trial
  • have ALL that has come back or got worse after a stem cell transplant Open a glossary item that was more than 100 days ago and you have no sign of graft versus host disease Open a glossary item and you have stopped taking medication to damp down your immune system Open a glossary item for at least a week
  • have ALL that has come back or got worse after having CAR T cell therapy and it has been at least 4 weeks since you had the CAR T cells
  • have satisfactory blood test results
  • are at least able to be up and about for half the day and can look after yourself (performance status 0 to 2) if you are 18 years or older or you are at least up and about for most of the time, active play is minimal but you can mostly take care of yourself (Lansky play scale 60 or more; Karnofsky performance score 60 or more) if you are younger than 18 years old
  • need to be a certain size to take part (your doctor will work this out)
  • are willing to use reliable contraception during treatment and for at least 4 weeks afterwards for women and 12 weeks afterwards for men if there is any chance you or your partner could become pregnant
  • are able to swallow the selumetinib capsules whole

You cannot join this trial if any of these apply.

Cancer related
You:

  • have ALL that doesn’t have the gene change in the RAS-pathway
  • have mature B cell leukaemia
  • have ALL that has the Philadelphia chromosome Open a glossary item
  • still have moderate to severe side effects from any previous anti cancer treatment apart from hair loss
  • have had an anti cancer drug that works in a similar way to selumetinib
  • have had an experimental drug as part of a clinical trial or any other anti cancer treatment (apart from dexamethasone and hydroxycarbamide) that affects your whole body (systemic treatment) within the 4 weeks of joining the trial (6 weeks for nitrosoureas Open a glossary item, suramin and mitomycin)
  • have had radiotherapy within 4 weeks of joining the trial or within 7 days of starting your treatment if it is a small area of radiotherapy for relief of pain (palliative) 
  • have any other cancer that your doctor think could affect you taking part

Medical condition
You:

  • have severe heart problems such as angina, heart failure or your heart isn’t working well enough
  • have or had eye problems such as an increased pressure in the eye, a blocked vein in the eye or glaucoma that isn’t controlled by medication
  • have had major surgery within 4 weeks of joining the trial apart from surgery to put in a central line Open a glossary item or similar device
  • are allergic to selumetinib, dexamethasone, any of their ingredients or any similar types of drug
  • have any problems with your digestive system Open a glossary item, such as uncontrolled vomiting, irritable bowel syndrome or bowel surgery, that would affect how you absorb tablets or capsules
  • have HIV, hepatitis B or hepatitis C
  • have kidney problems or have had a kidney transplant
  • have an infection needing treatment
  • have a bleeding problem that isn’t controlled
  • have any other medical or mental health condition that could affect you taking part

Other
You:

  • are pregnant or breastfeeding

Trial design

Before starting treatment in this trial, the team need to find out if your leukaemia has a gene change (mutation) in the RAS-pathway. You will have a bone marrow test Open a glossary item to check for this.

You can’t take part in this trial if your ALL doesn’t have the gene change in the RAS-pathway. Your doctor will then talk to you about any other possible treatment you might have. 

This is a phase 1/2 trial. Everyone taking part will have selumetinib and dexamethasone. The team need up to 42 people to take part.

There are 2 parts to this trial.

Part 1
In this part the researchers want to find the highest safe dose of selumetinib to give with dexamethasone.

The first few people will have a low dose of selumetinib with dexamethasone. The next group of people will have a higher dose if the first didn’t have any bad side effects. And so on until the researchers have found the best dose of selumetinib to give with dexamethasone. This is called a dose escalation study.

Part 2
In this part everyone has the best dose of selumetinib to give with dexamethasone.

You take selumetinib capsules twice a day. Your doctor will tell you how many to take. You continue to take selumetinib throughout the trial.

You take dexamethasone every day for 4 weeks. Then you have it during the first week for each 4 week period.

You can continue treatment for up to 6 months if you don’t have any bad side effects and it is helping you.

You have a diary to fill in when you have selumetinib and how many. You must bring this with you every time you go to the hospital.

Other treatment
You will have a test called a lumbar puncture Open a glossary item. This is to see if your leukaemia has gone into the fluid surrounding your spinal cord and brain. If it has you will have a chemotherapy drug called methotrexate injected into the fluid. This is a standard treatment Open a glossary item for leukaemia cells in the spinal fluid.

Blood samples
The researchers will take extra blood samples when you first start selumetinib. They will use these to find out what happens to selumetinib in your body and how your body deals with it.

Hospital visits

You see the doctor and have some tests when you agree to join the trial. These tests include:

  • a physical examination
  • blood tests
  • urine test
  • bone marrow test
  • lumbar puncture
  • heart trace (ECG Open a glossary item)
  • heart scan (ECHO Open a glossary item)
  • eye examination (done by an eye specialist)

At the start of treatment you see the doctor every week for 4 weeks for:

  • blood tests
  • urine test
  • a physical examination

You have another heart trace when you start treatment.

At 4 weeks you have a:

  • heart scan
  • bone marrow test
  • lumbar puncture if your first lumbar puncture showed there were leukaemia cells in the spinal fluid

After this, you see your doctor every 4 weeks during treatment.

You have a bone marrow test at 12 weeks and 24 weeks of treatment.

You might have further eye examinations or heart scans if your doctor thinks you need them.

At the end of treatment, you see the doctor for the same tests you had at the start and another bone marrow test.

After treatment you see the doctor after 1 month for:

  • a physical examination
  • blood tests
  • urine test
  • heart trace

Side effects

Your doctor and nurse will monitor you closely for any side effects. Let your doctor or nurse know as soon as possible if:

  • you have severe side effects
  • your side effects aren’t getting any better
  • your side effects are getting worse

As early treatment can help manage side effects better, especially for diarrhoea and sickness.

Selumetinib is a new drug and there might be side effects we don’t know about yet.

The most common side effects of selumetinib we know of so far include:

Information from early research shows that people of Asian origin may have higher levels of selumetinib in their blood than other people. And this might cause them to have more side effects than others.

Methotrexate into the fluid around the spine and brain is a standard treatment. And it has been used for several decades. Side effects are rare and you will be monitored closely while having this treatment.

The side effects include:

  • headache
  • feeling or being sick
  • stiff neck

A delayed side effect can be changes to the brain (encephalopathy) that can cause:

  • fits (seizures)
  • changes to the level of consciousness

We have information about the side effects of:

Your doctor will talk to you about the side effects of all the treatments in this trial before you agree to take part.

Location

Birmingham
Liverpool
London
Manchester
Sheffield
Sutton

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

Dr Tobias Menne

Supported by

AstraZeneca
Cancer Research UK
University of Birmingham

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14315

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

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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