REMIT
Research type
Research Study
Full title
RadiotheRapy priMIng for CAR-T
IRAS ID
295832
Contact name
Andrea Kuhnl
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary:
This trial is testing bridging radiotherapy prior to tisagenlecleucel chimeric antigen receptor T-cell therapy (CAR-T) for patients with aggressive non-Hodgkin lymphoma (diffuse large B-cell lymphoma) which has not responded to prior treatment or has relapsed. CAR T-cells are manufactured from patient’s own white blood cells, a process which takes around six weeks. Treatments used to control and reduce lymphoma during this period are called bridging therapies. Effective bridging allows patients to remain well enough to proceed to CAR T-cell therapy and may lead to improved responses and fewer serious side effects. This trial will assess whether it is possible to give bridging radiotherapy, planned and given according to the amount of lymphoma in different parts of the body (known as the metabolic tumour volume, assessed on a PET scan), without delaying the CAR T-cell treatment.
Radiotherapy is already used as bridging therapy, but no standard protocols exist, and it has not been assessed in a clinical trial. In this trial a higher dose of radiotherapy will be given to larger areas of lymphoma with potential to cause symptoms, and a lower dose to smaller areas of lymphoma. The total radiotherapy dose will be equivalent to doses used in standard practice. This aims to give the best reduction in the lymphoma volume before CAR T-cell therapy, and it is also thought that the effect of radiotherapy on the treated areas and on the immune system may improve how well the CAR T-cell therapy works.
Radiotherapy will be given 5 days per week and the duration will depend on the individual treatment plan. There will be a minimum gap of 14 days after radiotherapy before CAR-T cell therapy. All subsequent care will be given according to standard practice in the treating hospital and there should be no change in the overall duration of lymphoma treatment.
Lay summary of study results:
The REMIT trial looked at whether radiotherapy could be safely and practically used as a treatment before CAR T-cell therapy in people with large B-cell lymphoma that had returned or had not responded to previous treatment.
CAR T-cell therapy is a type of treatment in which some of a patient's own immune cells are collected and modified in a laboratory so that they can recognise and attack cancer cells. There is a period of several weeks between collecting the cells and giving the CAR T-cell treatment. During this time, patients may need treatment to keep their lymphoma under control. This is known as "bridging treatment".
REMIT investigated an individualised approach to radiotherapy as bridging treatment. PET scans were used to assess the amount and location of lymphoma in each patient and to help decide which areas should receive radiotherapy and what dose should be given.
The trial planned to recruit 20 patients but closed early after 6 patients had been registered. This was because the CAR T-cell treatment being used in the trial, tisagenlecleucel (tisa-cel), has been used far less in the UK over time which led the manufacturer to withdraw it from the UK market, even though tisa-cel remains licenced and used in other countries.
All 6 patients received the planned radiotherapy. The main aim of the trial was to find out whether radiotherapy could be given without delaying the next stage of treatment before CAR T-cell therapy. No delays caused by radiotherapy were reported.
Side effects related to radiotherapy were mild. These included inflammation and soreness of the mouth or throat and nausea. One of the 6 patients did not go on to receive CAR T-cell therapy because of an existing heart condition rather than because of the radiotherapy.
Because the trial closed early and only a small number of patients took part, it was not possible to answer all of the questions originally planned. However, the results suggest that this individualised approach to radiotherapy can be given as bridging treatment without delaying CAR T-cell therapy and with few radiotherapy-related side effects.
The researchers also looked at outcomes from an additional 7 patients who were not part of the REMIT trial but received a similar approach to radiotherapy before a different CAR T-cell treatment. Results from all 13 patients provided additional information supporting the feasibility of this approach. However, these additional patients were not participants in the REMIT trial and their results should therefore be considered separately from the trial results.
Further research involving larger numbers of patients would be needed to determine whether this approach improves outcomes following CAR T-cell therapy.REC name
London - Surrey Research Ethics Committee
REC reference
21/LO/0714
Date of REC Opinion
15 Oct 2021
REC opinion
Favourable Opinion