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New treatment for relapsed follicular lymphoma

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

PHASE2 · University of Birmingham · NCT05848765

This study is testing a new treatment combining epcoritamab and lenalidomide for people with relapsed follicular lymphoma to see if it works better than the usual treatments.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment284 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity of Birmingham (other)
Drugs / interventionsrituximab, obinutuzumab, CAR-T, chemotherapy, immunotherapy, doxorubicin, epcoritamab
Locations25 sites (Aberdeen and 24 other locations)
Trial IDNCT05848765 on ClinicalTrials.gov

What this trial studies

The REFRACT clinical trial aims to evaluate new therapies for patients with relapsed or refractory follicular lymphoma by comparing an experimental treatment, epcoritamab combined with lenalidomide, against standard treatment options chosen by the physician. Patients will be randomly assigned to receive either the experimental treatment or one of five standard therapies over three treatment rounds. The study will recruit 284 patients over five years, assessing the effectiveness of the new treatment compared to existing options.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and over with biopsy-proven relapsed or refractory CD20 positive follicular lymphoma requiring treatment.

Not a fit: Patients with non-CD20 positive follicular lymphoma or those who have not received prior immunochemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a more effective treatment option for patients with relapsed or refractory follicular lymphoma.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination of treatments is being evaluated for the first time.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma (biopsy within 3 months of trial entry)
2. Aged 18 years or over
3. Advanced disease that in the opinion of the treating physician requires treatment
4. Patient suitable for standard available therapy at the Investigator's discretion
5. 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
6. Assessable disease by PET-CT (at least one involved node with long diameter \>1.5cm, or extranodal lesion \>1cm )
7. ECOG performance status of 0, 1 or 2 at trial entry
8. 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
9. Able to provide written informed consent
10. Women of childbearing potential (or their partners) must use an effective form of contraception

Exclusion Criteria:

1. 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)
2. Non-Fluorodeoxyglucose (FDG) avid disease
3. Prior allogenic stem cell transplantation (SCT) or solid organ transplant
4. Prior treatment with lenalidomide
5. Treatment with CAR-T therapy within 100 days of starting trial treatment
6. SCT or maintenance therapy planned within 24 weeks of starting treatment (patients planning SCT/maintenance after at least 24 weeks of treatment are eligible)
7. Immunochemotherapy with a platinum-containing regimen planned
8. Known serological positivity for HIV or uncontrolled HCV
9. 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
10. 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
11. Active systemic infection requiring treatment
12. Current or prior CNS involvement with lymphoma
13. History of allergy or anaphylaxis to anti-CD20 monoclonal antibody therapy
14. 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.
15. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
16. 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
17. 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)
18. Women who are pregnant or breastfeeding
19. Prior treatment with the experimental therapy under investigation
20. Major surgery within 30 days of starting treatment
21. 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

Where this trial is running

Aberdeen and 24 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Relapsed Follicular Lymphoma, Refractory Follicular Lymphoma, Epcoritamab, Lymphoma

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.