The aim of the REFRACT clinical trial is to find new therapies with improved outcomes compared to the current standard treatment available, in patients with relapsed or refractory follicular lymphoma. This will be done by comparing patients who have received a new treatment against patients who receive standard treatment based on their response to the treatment received.
In the REFRACT trial patients with relapsed or refractory follicular lymphoma (rrFL) will be randomised (randomly allocated) to receive a new treatment (experimental treatment) or standard treatment which will be chosen by their doctor prior to entering the trial (called investigator choice standard therapy (ICT)). There are 3 treatment rounds which will happen one after another, testing 3 different experimental treatments. The experimental treatment in each round will be compared to ICT. ICT will be a choice of 1 of 5 standard treatment options including RCHOP, RCVP, lenalidomide and rituximab, bendamustine and rituximab or obinutuzumab and bendamustine. Patients in Round 1 (R1) will be randomised using a 1:1 allocation ratio (meaning patients have a 50/50 chance of receiving the experimental treatment). In Round 1 the experimental treatment is epcoritamab combined with lenalidomide. Patients randomised to epcoritamab and lenalidomide will receive up to 12 28-day cycles of therapy; epcoritamab will be delivered as a subcutaneous injection weekly for cycles 1 and 2 and on day 1 of cycles 3-12. Lenalidomide will be taken orally on days 1-21 of each cycle. Patients in Rounds 2 (R2) and 3 (R3) (experimental treatments yet to be determined) will be randomised using a 1:4 allocation ratio in favour of the experimental treatment (meaning patients are more likely to receive the experimental treatment). The study will recruit 284 patients with rrFL over 5 years. The aim is to identify new therapies which have better outcomes compared to ICT based on patients response to treatment (tested by PET scan) after 24 weeks of therapy. Following treatment patients will be followed up yearly until the end of the trial (up to 10 years).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
Bispecific antibody
Immunomodulatory agent
Monoclonal antibody
Complete metabolic response (CMR)
CMR will be assessed by PET-CT using the Deauville 5-point scale and Lugano 2014 criteria. Patients who die from any cause or relapse/progress prior to this time-point will be considered non-responders. Patients who don't have a PET-CT scan within the protocol defined window or withdraw from the trial prior to this time-point will be considered non outcome evaluable. Patients who undergo stem-cell transplant (SCT) within 24 weeks of randomisation, patients who fail to start treatment and patients whose ineligibility is deemed to impact upon response to treatment will be replaced and hence not included in the analysis of this outcome
Time frame: 24 weeks
Overall metabolic response
Complete metabolic response (CMR) and partial metabolic response (PMR) will be assessed by PET-CT. Patients who die from any cause or relapse/progress prior to this time-point will be considered non-responders. Patients who undergo stem-cell transplant (SCT) within 24 weeks of randomisation, patients who fail to start treatment and patients whose ineligibility is deemed to impact upon response to treatment will be replaced and hence not included in the analysis of this outcome
Time frame: 24 weeks
Progression free survival (PFS)
The time from randomisation to the date of first disease progression or death. Patients who are alive and relapse/progression at the time of analysis will be censored at their date last seen
Time frame: 10 years
Overall survival (OS)
The time from randomisation to the date of death from any cause. Patients who are alive at the time of analysis will be censored at their date last seen
Time frame: 10 years
Duration of response (DoR)
The time from complete and partial metabolic response by PET-CT to relapse/progression or death from any cause. Patients who are alive and relapse/progression free at the time of analysis will be censored at their date last seen
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NONE
Enrollment
284
Monoclonal antibody
Alkylating agent (chemotherapy drug)
Antineoplastic, Vinca Alkaloid
Anthracycline
Alkylating agent (chemotherapy drug)
Corticosteroid
The drug used in round 2 is yet to be confirmed, round 2 is estimated to open in Q4 2025 and the record will be updated when the drug has been confirmed
The drug used in round 3 is yet to be confirmed, round 3 is estimated to open in Q3 2027 and the record will be updated when the drug has been confirmed
NHS Grampian
Aberdeen, United Kingdom
NOT_YET_RECRUITINGBelfast Health & Social Care Trust
Belfast, United Kingdom
NOT_YET_RECRUITINGUniversity Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
NOT_YET_RECRUITINGBlackpool Teaching Hospitals NHS Foundation Trust
Blackpool, United Kingdom
NOT_YET_RECRUITINGCambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom
NOT_YET_RECRUITINGCardiff and vale University LHB
Cardiff, United Kingdom
NOT_YET_RECRUITINGUniversity Hospitals Coventry and Warwickshire NHS Trust
Coventry, United Kingdom
NOT_YET_RECRUITINGCroydon Health Services NHS Trust
Croydon, United Kingdom
NOT_YET_RECRUITINGNHS Greater Glasgow and Clyde
Glasgow, United Kingdom
NOT_YET_RECRUITINGThe Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
NOT_YET_RECRUITING...and 15 more locations
Time frame: 10 years
Duration of complete response (DoCR)
The time from complete metabolic response by PET-CT to relapse/progression or death from any cause. Patients who are alive and relapse/progression free at the time of analysis will be censored at their date last seen
Time frame: 10 years
Time to next treatment (TTNT)
The time from randomisation to the start date of next treatment for lymphoma. Patients who are responding (CMR or PMR) who receive consolidation radiotherapy will not be considered an event and will be censored at their date last seen if no other treatment for lymphoma is reported. Patients who die without having started next lymphoma treatment will be considered a competing risk at their date of death, and patients who are alive and have not started next lymphoma treatment at the time of analysis will be censored at their date last seen
Time frame: 10 years
Adverse events (AEs)
Collected and reported in accordance with CTCAE version 5 defined as the number of patients who experience one or more grade 3 or 4 adverse events or serious adverse events of any grade
Time frame: Collected from start of treatment until 60 days after treatment
Quality of Life (QoL)
Measured using the EQ-5D-5L and FACT-Lym
Time frame: Collected pre-treatment, day 1 of cycle 3 (28 day cycles), 24 weeks from treatment start and then every 24 weeks in non-progressed patients until the end of the study (10 years)
Quality of Life (QoL)
Measured using the FACT-Lym
Time frame: Collected pre-treatment, day 1 of cycle 3 (28 day cycles), 24 weeks from treatment start and then every 24 weeks in non-progressed patients until the end of the study (10 years)