Choices trial

ChOICES - CHlorOquine and Imatinib Combination to Eliminate Stem cells

A Randomised phase II trial of Imatinib (IM) versus hydroxycholorquine (HCQ) and IM for patients with Chronic Myloid Leukaemia (CML) in Major Cytogenetic Response (MCyR) with residual disease detectable by quantitative polymerase chain reaction (Q-PCR).

Research Summary
This is a randomised phase 2 trial with a safety run-in, designed to study the safety and efficacy of HCQ in combination with Imatinib. CML CP patients who are in MCyR after >1 and <3 years of Imatinib treatment and tolerating Imatinib well will be randomised between Imatinib alone and Imatinib and HCQ 800mg/day. Imatinib will be given at the patient’s current stable dose. Treatment will be given continuously. Treatment with IM + HCQ will be continued for 12 cycles to further study tolerance and to study the efficacy of the combination to reduce or eliminate BCR/ABL+ cells. 33 patients will be randomised to each treatment to a total of 66 patients, recruited in 3 centres. Time required for accrual of all patients is anticipated to be 24 months. Time on study IM + HCQ treatment for each patient is 12 months. Follow-up assessments for each patient continue to 24 months. All patients will continue on their daily dose of Imatinib treatment that they were receiving prior to entry in the trial.

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Further information:
I have provided an edited version of an overview of the CHOICES trial. It is thought that Hydroxychloroquine has an effect on the quiescent (inactive/sleeping state) leukaemic stem cell.
Professor Holyoake has been the lead in this research over the last 10 years.

I understand that the possible effect on eyesight is extremely rare. see info for Chloroquine from wikipaedia here

wikipedia.org/wiki/Chloroquine

Sandy

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A trial of hydroxychloroquine with imatinib for chronic myeloid leukaemia (CHOICES)

This trial is looking at adding a drug called hydroxychloroquine to treatment for chronic myeloid leukaemia (CML) that has already responded well to imatinib.

The people taking part in this trial have had a good response to imatinib, but their doctors can see there are still some cancer cells by doing a PCR test. Everybody taking part will carry on having imatinib, but some people will also start taking a drug called hydroxychloroquine.

Hydroxychloroquine is already used to treat other diseases such as rheumatoid arthritis. Doctors think it may also help to get rid of residual disease in chronic myeloid leukaemia.

The aims of the trial are to

See if imatinib with hydroxychloroquine is better at reducing the number of residual leukaemia cells than imatinib alone
Learn more about the side effects

Recruitment
Start 01/04/2010
End 30/09/2013

Phase 2
You can enter this trial if you

Were diagnosed with chronic myeloid leukaemia in chronic phase and have been taking imatinib for at least 1 year and are on a stable dose
Have had a good response to imatinib (this is called a major cytogenetic response and your doctor can confirm this for you)
Have leukaemia cells with a genetic change that doctors can monitor using a PCR test
Have been taking the same dose of imatinib for at least 6 months
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 the trial and for 3 months afterwards if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you:
Are currently having radiotherapy or any other cancer treatment
Have had major surgery, chemotherapy or an experimental drug in the last 4 weeks (or have not recovered from side effects of earlier treatment)
Have an eye condition called maculopathy
Have high blood pressure that cannot be controlled with medication
Have heart failure, another heart problem that is a cause for concern, or any other serious medical condition (the trial doctors can advise you about this)
Are pregnant or breastfeeding.

Trial design
This is a randomised trial. The people taking part are put into 1 of 2 treatment groups by a computer.

Neither you nor your doctor will be able to decide which group you are in.

Half the people taking part will just carry on taking imatinib.

The other half will carry on taking imatinib, but will also have hydroxychloroquine. They take it as a tablet twice a day, for up to a year.

The researchers will take extra blood samples from some people taking part to learn more about what happens to both drugs in the body.

This is called pharmacokinetics.

They will also ask 10 people in each group to have 2 extra bone marrow tests. This is to see if having both drugs together works better than having imatinib alone.

Hospital visits
You will see the doctors and have some tests at the beginning of the trial. The tests include

Physical examination including an eye test
Blood tests
Heart trace (ECG)
Bone marrow test

People taking hydroxychloroquine will have another ECG after 6 weeks of treatment, and they have regular eye tests during the trial.

Everybody taking part goes to see the trial team weekly for the first 4 weeks, every 2 weeks for the next 4 weeks, and then once every 4 weeks for nearly a year.

After a year, you have follow up appointments every 3 months for the next 12 months.

Side effects
The possible side effects of hydroxychloroquine include:

Skin rash
Feeling sick
Diarrhoea
Headache

Very rarely, if you take hydroxychloroquine for a long period of time, it can affect your eyesight. So, people taking it in this trial have regular eye tests.

There is more information about possible side effects of imatinib on CancerHelp UK. There may be some side effects caused by having both drugs at the same time that doctors don’t know about yet.

Locations of trial:
Cambridge
Dumfries
Glasgow
Liverpool
London
Nottingham

Chief Investigator
Professor Tessa Holyoake
Supported by
Cancer Research UK Clinical Trials Unit, Glasgow
Experimental Cancer Medicine Centre (ECMC)
Medical Research Council (MRC)
National Institute for Health Research Cancer Research Network (NCRN)