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Relapsed Follicular LymphomaPhase 2REFRACTNCT05848765

Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy

A Phase 2 study testing Epcoritamab, Lenalidomide and Rituximab in people with Relapsed Follicular Lymphoma and Refractory Follicular Lymphoma, run by University of Birmingham at 25 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Epcoritamab, Lenalidomide and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
284 participants
Where
25 sitesUnited Kingdom
Study dates
4 Sep 2023to 30 Nov 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma (biopsy within 3 months of trial entry)
  • Aged 18 years or over
  • Advanced disease that in the opinion of the treating physician requires treatment
  • Patient suitable for standard available therapy at the Investigator's discretion
  • Prior therapy with at least one line of immunochemotherapy. Previous radiotherapy at any time is permitted and will not count as a line of therapy. Previous rituximab monotherapy is also permitted as long as patients have at any time also received at least one line of immunochemotherapy
  • Assessable disease by PET-CT (at least one involved node with long diameter >1.5cm, or extranodal lesion >1cm )
Show all 10Show fewer
  • ECOG performance status of 0, 1 or 2 at trial entry
  • Adequate organ function defined as; i. ANC ≥ 1.0 x 109/L (growth factor use is permitted) ii. Platelet count ≥ 75 x 109/L, or ≥ 50 x 109/L if bone marrow infiltration or splenomegaly iii. ALT and AST level ≤3 x ULN iv. Direct bilirubin level ≤ 2 x ULN, unless due to Gilbert's syndrome v. CrCl ≥ 50mL/min (by Cockcroft-Gault formula) vi. PT, INR and aPTT ≤ 1.5 x ULN, unless receiving anticoagulation vii. LVEF within normal limits by MUGA or echocardiography
  • Able to provide written informed consent
  • Women of childbearing potential (or their partners) must use an effective form of contraception

Who cannot join

  • Current (or within 1 year) transformation to high grade lymphoma, including grade 3b follicular lymphoma (patients with historical high-grade transformation over 1 year ago are eligible)
  • Non-Fluorodeoxyglucose (FDG) avid disease
  • Prior allogenic stem cell transplantation (SCT) or solid organ transplant
  • Prior treatment with lenalidomide
  • Treatment with CAR-T therapy within 100 days of starting trial treatment
  • SCT or maintenance therapy planned within 24 weeks of starting treatment (patients planning SCT/maintenance after at least 24 weeks of treatment are eligible)
Show all 21Show fewer
  • Immunochemotherapy with a platinum-containing regimen planned
  • Known serological positivity for HIV or uncontrolled HCV
  • Hepatitis B surface antigen (HBsAg) positive and/or detectable viral DNA. Patients positive for Hepatitis B core antibody (anti-HBc) but viral DNA negative are eligible
  • Other malignancy within 2 years of enrolment, excepting cervical carcinoma stage 1B or less, non-invasive basal cell or squamous cell skin carcinoma, non-invasive, superficial bladder cancer, prostate cancer with a current PSA level <0.1ng/mL, any curable cancer with a CR of > 2 years duration
  • Active systemic infection requiring treatment
  • Current or prior CNS involvement with lymphoma
  • History of allergy or anaphylaxis to anti-CD20 monoclonal antibody therapy
  • Known hypersensitivity to any of the experimental arm IMPs. Patients with a known hypersensitivity to a control arm regimen may still be eligible if they have no hypersensitivity to other potential control arm IMPs.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Recent cancer treatment (chemotherapy, immunotherapy, biological therapy) within 4 weeks of starting trial treatment; systemic steroid treatment (prednisolone > 10mg daily (or equivalent)) within 7 days of cycle 1 day 1 dosing
  • Unwilling to use appropriate contraception methods whilst on study treatment and for 12 months following end of treatment (or 18 months for female patients whose ICT regimen contains obinutuzumab)
  • Women who are pregnant or breastfeeding
  • Prior treatment with the experimental therapy under investigation
  • Major surgery within 30 days of starting treatment
  • Severe arrhythmias, heart failure, previous myocardial infarction, acute inflammatory heart disease for ICT regimen containing doxorubicin, or severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease for ICT regimen containing rituximab

Trial locations and contacts

25 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Trial Coordinator contact

0121 371 7861

refract@trials.bham.ac.uk

25 sites in 1 country

United Kingdom25 sites, 25 recruiting

  • NHS Grampian

    Aberdeen

    Not yet recruiting

  • Belfast Health & Social Care Trust

    Belfast

    Not yet recruiting

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham

    Not yet recruiting

  • Blackpool Teaching Hospitals NHS Foundation Trust

    Blackpool

    Not yet recruiting

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge

    Not yet recruiting

  • Cardiff and vale University LHB

    Cardiff

    Not yet recruiting

  • University Hospitals Coventry and Warwickshire NHS Trust

    Coventry

    Not yet recruiting

  • Croydon Health Services NHS Trust

    Croydon

    Not yet recruiting

  • NHS Greater Glasgow and Clyde

    Glasgow

    Not yet recruiting

  • The Leeds Teaching Hospitals NHS Trust

    Leeds

    Not yet recruiting

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Liverpool

    Not yet recruiting

  • Guy's and St Thomas' NHS Foundation Trust

    London

    Not yet recruiting

  • King's College Hospital NHS Foundation Trust

    London

    Not yet recruiting

  • The Royal Marsden NHS Foundation Trust

    London

    Not yet recruiting

  • University College London Hospital NHS Foundation Trust

    London

    Not yet recruiting

  • The Christie NHS Foundation Trust

    Manchester

    Recruiting

  • The Newcastle Upon Tyne Hospitals NHS Foundation Trust

    Newcastle

    Not yet recruiting

  • Norfolk and Norwich University Hospitals NHS Foundation Trust

    Norwich

    Not yet recruiting

  • Nottingham University Hospitals NHS Trust

    Nottingham

    Recruiting

  • Oxford University Hospitals NHS Foundation Trust

    Oxford

    Not yet recruiting

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield

    Not yet recruiting

  • University Hospital Southampton NHS Foundation Trust

    Southampton

    Not yet recruiting

  • University Hospital of North Midlands NHS Trust

    Stoke-on-Trent

    Not yet recruiting

  • Swansea Bay University Local Health Board

    Swansea

    Not yet recruiting

  • Torbay and South Devon NHS Foundation Trust

    Torquay

    Not yet recruiting

Other trials in United Kingdom

About this study

Official title: Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy (REFRACT): A Randomised Phase II Trial of Investigator Choice Standard Therapy Versus Sequential Novel Therapy Experimental Arms

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.

Read the detailed description

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).

Being tested
Epcoritamab, Lenalidomide, Rituximab, Obinutuzumab, Bendamustine
Keywords
Epcoritamab, Lymphoma
Medical subject headings
Lymphoma, Follicular, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EpcoritamabDrug

    Bispecific antibody

  • LenalidomideDrug

    Immunomodulatory agent

  • RituximabDrug

    Monoclonal antibody

  • ObinutuzumabDrug

    Monoclonal antibody

  • BendamustineDrug

    Alkylating agent (chemotherapy drug)

  • VincristineDrug

    Antineoplastic, Vinca Alkaloid

  • DoxorubicinDrug

    Anthracycline

  • CyclophosphamideDrug

    Alkylating agent (chemotherapy drug)

  • PrednisoneDrug

    Corticosteroid

  • Investigation agent 2Drug

    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

  • Investigation agent 3Drug

    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

Study groups in NCT05848765
Study groupRoleWhat they receive
Round 1: Epcoritamab and lenalidomideExperimentalEpcoritamab (weekly for cycles 1 and 2 and on day 1 of cycles 3-12 for up to 12 cycles) and lenalidomide (daily for days 1-21 of each cycle for up for 12 cycles), cycles will be 28 day cycles.
Receives: Drug: Epcoritamab; Drug: Lenalidomide
Round 2ExperimentalInvestigation agent 2
Receives: Drug: Investigation agent 2
Round 3ExperimentalInvestigation agent 3
Receives: Drug: Investigation agent 3
All rounds: Investigator Choice TherapyActive comparatorChoice of therapy to be selected by the Investigator for each patient prior to randomisation. The Investigator will choose between; RCHOP, RCVP, rituximab and bendamustine, rituximab and lenalidomide or bendamustine and obinutuzumab.
Receives: Drug: Lenalidomide; Drug: Rituximab; Drug: Obinutuzumab; Drug: Bendamustine; Drug: Vincristine; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 24 weeks

Secondary outcomes (9)

  1. 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

    Measured: 24 weeks

  2. 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

    Measured: 10 years

  3. 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

    Measured: 10 years

  4. 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

    Measured: 10 years

  5. 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

    Measured: 10 years

  6. 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

    Measured: 10 years

  7. 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

    Measured: Collected from start of treatment until 60 days after treatment

  8. Quality of Life (QoL)

    Measured using the EQ-5D-5L and FACT-Lym

    Measured: 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)

  9. Quality of Life (QoL)

    Measured using the FACT-Lym

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2023
  2. Study start4 Sep 2023
  3. Primary completion31 May 2029 (estimated)
  4. Study completion30 Nov 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
284 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05848765
Sponsor's protocol ID
RG_22-020
Acronym
REFRACT
Status last verified
Apr 2026
First submitted
18 Apr 2023
Last updated
5 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gaskell C, Linton K, Bishton M, McIlroy G, Lax S, Fox S, Hopkins L, Collings R, Rhodes M, Seale T, Jackson A. The REFRACT trial: implementation of Bayesian power priors in a randomised, sequential phase II adaptive platform trial. BMC Med Res Methodol. 2025 May 3;25(1):121. doi: 10.1186/s12874-025-02575-5.

    PubMed 40319227

  • McIlroy G, Lax S, Gaskell C, Jackson A, Rhodes M, Seale T, Fox S, Hopkins L, Okosun J, Barrington SF, Ringshausen I, Ramsay AG, Calaminici M, Linton K, Bishton M. Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial. BMC Cancer. 2024 Mar 25;24(1):370. doi: 10.1186/s12885-024-12112-0.

    PubMed 38528445

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Epcoritamab, Lenalidomide and Rituximab in people with Relapsed Follicular Lymphoma and Refractory Follicular Lymphoma, run by University of Birmingham at 25 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Trial Coordinator (0121 371 7861, refract@trials.bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete metabolic response (CMR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05848765, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.

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