Research project
FiTNEss (Myeloma XIV)
- Start date: 4 August 2020
- End date: 30 August 2027
- Primary investigator: Professor Gordon Cook
- Co-investigators: Dr Christopher Parrish, Professor David Cairns, Anna Hockaday
- External co-investigators: Prof. Graham Jackson (PI), Newcastle, Professor Mark Drayson, Dr Roger Owen, Dr Martin Kaiser, Dr John Jones, Ms Bryony Dawkins, Dr Ruth De Tute, Dr David Meads, Dr Charlotte Pawlyn, Dr Jenny Bird, Dr Stella Bowcock, Dr Matthew Jenner, Dr Bhuvan Kishore, Dr Neil Rabin
Description
Funded by CRUK/Takeda/BMS
A blinded randomised controlled trial of frailty score-adjusted dosing of the combination ixazomib, lenalidomide and dexamethasone and the use of lenalidomide and ixazomib maintenance therapy in newly diagnosed, non-transplant eligible patients with multiple myeloma.
What is the FITNEss trial?
FiTNEss (also known as Myeloma XIV) is a cancer trial for patients with multiple myeloma. Multiple myeloma is a cancer of plasma cells. Plasma cells are white blood cells that are made in the bone marrow and help fight harmful bacteria and viruses in your blood. Patients with myeloma have plasma cells that do not work properly. Some people have a stem cell transplant as a treatment for myeloma. This is a procedure where patients receive healthy stem cells to replace damaged stem cells. This is an intensive treatment and not suitable for everyone. This trial was intended for patients who cannot have a bone marrow transplant and is split into two stages (described below)
How are people recruited to the trial?
Before patients begin the trial, their doctor needs to first make sure that they have multiple myeloma. To confirm that a patient has myeloma they have to have a bone marrow sample taken. The trial also needs a bone marrow sample to find out information about the patient’s myeloma. A bone marrow sample is an invasive test which can be painful. So that patients do not need to have multiple bone marrow samples, we ask patients whose doctor think they might have multiple myeloma if they would like to be considered for the trial. If they agree, it means part of their bone marrow sample can go to the trial’s laboratory. The sample will be ready if they enter the trial.
Once their doctor has confirmed they have multiple myeloma, patients are asked if they want to start Stage 1 of the trial. If they say yes, it is checked that it is safe for them to enter the trial. If they say no or do not have myeloma, they are treated by their doctor outside of the trial.
What is the first stage of the trial?
In the first stage, we look at treating patients with a combination of three medicines. These medicines combined are called IRD, consisting of ixazomib, lenalidomide (also called Revlimid) and dexamethasone. This is a common treatment for patients with multiple myeloma.
From past studies, we noticed a large proportion of elderly patients stop taking treatment within 60 days of starting it. Most patients stopped due to suffering from harmful side effects from their medicine. We call these harmful effects 'toxicities'. From this, we wondered if changing the starting dose based on how frail a patient is, can be used to reduce the fraction of patients stopping treatment early.
For the first stage, we ask each patient some questions to find out how frail they are. From this, we determine if a patient is either fit, unfit, or frail. We then randomly assign each patient to one of two treatment groups. We make sure that each group contains a mix of fit, unfit, and frail patients.
Both groups receive IRD. One group receives IRD with the same starting dose that they would receive outside of the trial. We call this ‘standard dosing’. Patients in the second group receive IRD at a lower starting dose if they are unfit or frail. We call this 'frailty-adjusted dosing'. We want to see if the patients receiving a smaller starting dose have less toxicities. However, they still need to be taking some medicine for it to help to treat their myeloma. Essentially, we are balancing the positive effect of the drugs with their inherent toxicities.
In both groups, we continue asking questions on how frail each patient is. This is so that we can adjust doses for the frailty score-adjusted dosing as needed. In both groups, doses can be changed for other reasons for the patient’s benefit. For example, doses might be reduced due to side effects of the treatment.
For this stage, our main goal is to look at the fraction of unfit and frail patients who stop taking IRD early. Patients stop taking IRD early if they stop within 60 days of starting. We compare this fraction between the standard and frailty-adjusted dosing. We hope that this fraction is much smaller for the frailty score-adjusted dosing. If so, we can say that this new way of dosing allows more patients to stay on treatment for longer.
What is the second stage of the trial?
Stage 1 lasts for about 12 months for a single patient. Patients who stay on this IRD treatment for the full length then continue to Stage 2 of the trial. For this stage, we are also comparing two groups that receive different treatments. One group receives the medicines lenalidomide and ixazomib (R + I). The other group receives lenalidomide and a placebo (a treatment with no effect), namely (R + placebo). We do this to find out whether taking R + I is more effective than taking R on its own. Patients are placed in one of the two groups by a process of randomisation (like flipping a coin).
Please note that the placebo does not affect patients’ health. Patients might feel better when taking more medicines, even when extra medicines would not improve a patients’ health. We use R + placebo instead of ‘R only’ to see if any changes are really due to the extra medicine. Patients and doctors will not know whether a patient is taking ixazomib or the placebo in order to avoid bias in influencing the results of the trial. This makes this part of the trial double-blind.
In the second stage, our main goal is to compare how long patients live without their myeloma getting worse. We call the time it takes for this to occur from starting treatment as 'progression free survival' (PFS). We compare PFS between R + I and R + placebo. If the combination R + I is more effective, then this time will be longer on average for patients taking R + I compared to R + placebo.
What else is the trial looking at?
In both stages of the trial, we are also looking at other comparisons between the different treatments. This includes:
- How long patients live for (survival),
- The side effects patients experience on treatment (toxicity and safety)
- How patients feel on the trial (quality of life)
- How a patient’s myeloma reacts to the treatment (response)
If you are a patient or a member of the public, and would like to know more about Leeds Institute of Clinical Trials Research (LICTR) where this trial was ran from or about clinical trial research in general please visit out CTRU Research Portal.
Publications and outputs
Conference Abstracts: