"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”
A study looking at adding a type of biological therapy to chemotherapy for acute lymphoblastic leukaemia that has not responded, or has come back after treatment (MARALL)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
This study is looking at the safety of adding the drugs veltuzumab and epratuzumab to chemotherapy to treat acute lymphoblastic leukaemia (ALL) that has either not responded to treatment, or has come back. This study is supported by Cancer Research UK.
The main treatment for acute lymphoblastic leukaemia is chemotherapy. If tests after treatment show that you have no leukaemia cells in your blood and bone marrow, doctors say that your leukaemia is in
This study is looking veltuzumab and epratuzumab, which are biological therapies called monoclonal antibodies. Monoclonal antibodies can seek out cancer cells by looking for particular proteins on the cell’s surface.
Veltuzumab seeks out a protein called CD20, and epratuzumab looks for the CD22 protein. When these antibodies attach to the protein, they kill the cell.
Veltuzumab and epratuzumab have been studied in clinical trials with chemotherapy, but not in people with ALL. The main aim of this study is to see if adding veltuzumab and epratuzumab to treatment for relapsed ALL is safe. If it is, researchers will plan further trials to help improve the treatment of people with ALL.
Who can enter
You can enter this study if you
- Have a type of acute lymphoblastic leukaemia (ALL) called Pre (precursor) B cell ALL
- Had treatment which put your ALL into
remission, but it has come back (your ALL has relapsed) or had treatment for your ALL, but it didn't respond (your ALL is refractory)
- Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- Have satisfactory blood tests
- Are willing to use reliable contraception during the study treatment and for 3 months afterwards if there is any chance that you or your partner could become pregnant
- Are at least 16 years old
You cannot enter this study if you have either
- Had treatment for relapsed ALL (you can still take part if you have taken steroids for fewer than 10 days - please note, you must not stop taking steroids without talking to your doctor first) OR
- Had chemotherapy in the last 7 days for ALL that has not responded to treatment (refractory ALL), or have not recovered from any side effects of your previous chemotherapy
- Have ALL that is
Philadelphia chromosomepositive, and you have either not had treatment with a type of drug called a tyrosine kinase inhibitor, or tests show that the number of Philadelphia positive cells that you have has increased after treatment, but this has not yet caused any symptoms
- Have had treatment with a monoclonal antibody in the last 3 months
- Have high blood pressure, diabetes, or any other condition which could make you unwell or affect the results of the study – you can check this with your doctor
- Are having medication as part of another clinical trial
- Are pregnant or breastfeeding
This phase 1/2 study will recruit up to 55 people. You will be put into one of 3 possible groups, depending on when you join the study. The first 2 groups are part of phase 1. If results are promising from this phase, the study team will move to phase 2 and open a third group. Everyone will have the same chemotherapy with either veltuzumab or epratuzumab, or both, depending on the group you are in.
The chemotherapy you have will be one that doctors often use to treat ALL that has come back or has not responded to treatment. Everyone will have one cycle of treatment which takes 29 days. You have
- Vincristine chemotherapy through a drip into a vein on days 1, 8, 15 and 22
- Dexamethasone tablets on days 1 to 5 and 11 to 14
- Methotrexate as an injection into the fluid around your spine (intrathecally) on day 24
Also, you may have 1 or 2 doses of peg-asparaginase (or a similar drug) either through a drip into a vein, or as an injection into a muscle on days 4 and 18 (whether you have this at all, or the number of doses you have, depends on your age, treatments you have had already and how your leukaemia responded to them).
If you are in group 1, you will have veltuzumab with your chemotherapy. If you are in group 2, you have epratuzumab with your chemotherapy. People in group 3 will have both.
You have veltuzumab or epratuzumab or both as a slow drip (infusion) into a vein, on days 8, 15, 22 and 29 of your chemotherapy cycle. If you are in group 3 you have both drugs on these days, one after the other.
You will have regular blood and urine tests throughout the study.
After the study you continue to see your usual leukaemia doctors in the same way as you did before. With your permission, the study team will check your medical notes regularly for 2 years to see how you are getting on.
Before you start treatment, you will see the doctor and have some tests. These tests include
- Bone marrow tests (bone marrow trephine and biopsy)
- Blood tests
- Lumber puncture
Heart trace (ECG)
- Urine test
- Pregnancy blood test (if appropriate)
You will have blood and urine tests regularly throughout the study, when you come for treatment.
At the end of your treatment you will repeat most of the tests you had at the start.
About 2 months after starting treatment you will see the study doctor and have a blood test. The study team will bring this appointment forward if you are due to start another treatment.
The tests and visits you have for the study are the same as if you were having the chemotherapy for relapsed or refractory ALL outside of the study. But you will give more samples at these visits than you would if you were not in the study.
Side effects of veltuzumab and epratuzumab include
- Fever and chills
- Severe tiredness (fatigue)
- Feeling sick
- Allergic reaction – this is rare, and staff will monitor you closely for this
- A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
You may have a bruise where you have your blood tests. You may also have some bleeding after your bone marrow biopsy.
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.
Dr Matthew Smith
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
Queen Mary University of London
This is Cancer Research UK trial number CRUK/08/040.