Reason for the study
Chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) are both types of cancer that affect the blood and bone marrow. There are lots of different kinds of treatment used to control these cancers, but most patients will receive biological therapies called tyrosine kinase inhibitors (TKIs) as their first treatment.
These treatments act on processes in the cancer cells and can stop them functioning properly, thus limiting their growth. They are very effective and can control disease for long periods of time. In some cases, the DNA in the cancer cells change by developing mutations. When this happens, the treatment a patient is receiving may stop working. There are thought to be over 100 mutations that affect the effectiveness of TKIs and some patients may have more than one mutation present. It is important to identify when a mutation is present so that treatments may be reviewed.
Currently we do not have accurate information on how common these mutations are in the UK, so this study is designed to help provide this information on using a new, more sensitive type of laboratory analysis called Next-Generation Sequencing.
Mutations in the cancer cells’ DNA have routinely been detected using a technique known as Sanger Sequencing (SS). However, in some cases the mutations may only be present in a few, but not all the cancer cells. These are called low-level mutations and may be missed by Sanger Sequencing.
A new technique called Next-Generation Sequencing (NGS), has become available. This is thought to give a higher level of sensitivity and can detect mutations when they are present in only 3% of cells (with Sanger Sequencing the mutation would have had to be present in over 20% of cells for it to be detected).
The information obtained from this study may help doctors to decide how to treat patients with these diseases in the future. The doctor may also decide to alter their patient’s treatment based on the results obtained from the blood sample.
To take part in the CALLS study, eligible patients will have CML or Ph+ALL and have a gene called BCR-ABL. This gene is detected in the blood and is used to diagnose and monitor CML and Ph+ALL. At entry into the study, patients should have a BCR-ABL 1 level of >0.1%.
What is involved and study visits
This study is aiming to recruit 400 patients from 40 centres across the UK, and it will be expected to take 18 months to recruit eligible patients.
This study will be available for adult patients (age ≥ 18 years) with CML (in all phases of disease) or Ph+ ALL with detectable BCR-ABL levels. Patients with CML will be on their first or subsequent TKI.
This study does not involve any trial medication; whichever medication or TKIs are given is decided by the patient’s haematologist and is not part of the study. There are no protocol-mandated procedures apart from the blood sample for mutation testing, which falls under current recommended clinical practice.
Patients who are eligible to enter the study will be given an information sheet which will provide an outline of the study and what this will involve. This will be followed by a discussion with their doctor and written consent obtained should the patient wish to go ahead.
Once this has been completed, a blood sample for mutation analysis will be required at the next available clinic visit. Study participation is expected to average approximately one month for each individual patient.
The blood sample will be sent by the research team at the patient’s local centre and processed at a central lab as part of the study procedures. The results of the blood sample that has been analysed at the central study lab will be sent to the patient’s consultant and specialist team. If any change in treatment is required, this will be determined by the patient’s own consultant haematologist and is not part of the study.
There are no further trial assessments to be completed, all information that is required for the study would be collected as part of current clinical practice and normal standard of care. This would include information about when the patient was diagnosed, medical history prior to diagnosis of CML/ALL and details of current treatment.
A summary of this clinical study will be available on: http://www.ClinicalTrials.gov. Talk to your medical team to find out more about this study and to see if you’re eligible to take part.