Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy

Last updated: November 28, 2023
Sponsor: University of Birmingham
Overall Status: Active - Recruiting

Phase

2

Condition

Lymphoma

Follicular Lymphoma

Treatment

Vincristine

Lenalidomide

Cyclophosphamide

Clinical Study ID

NCT05848765
RG_22-020
  • Ages > 18
  • All Genders

Study 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. 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.

Eligibility Criteria

Inclusion

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 atany time is permitted and will not count as a line of therapy. Previous rituximabmonotherapy is also permitted as long as patients have at any time also received atleast one line of immunochemotherapy
  6. Assessable disease by PET-CT (at least one involved node with long diameter >1.5cm, orextranodal 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 ispermitted) ii. Platelet count ≥ 75 x 109/L, or ≥ 50 x 109/L if bone marrowinfiltration or splenomegaly iii. ALT and AST level ≤3 x ULN iv. Direct bilirubinlevel ≤ 2 x ULN, unless due to Gilbert's syndrome v. CrCl ≥ 50mL/min (byCockcroft-Gault formula) vi. PT, INR and aPTT ≤ 1.5 x ULN, unless receivinganticoagulation 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 ofcontraception

Exclusion

Exclusion Criteria:

  1. Current (or within 1 year) transformation to high grade lymphoma, including grade 3bfollicular lymphoma (patients with historical high-grade transformation over 1 yearago 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 (patientsplanning 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. Patientspositive 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 orless, non-invasive basal cell or squamous cell skin carcinoma, non-invasive,superficial bladder cancer, prostate cancer with a current PSA level <0.1ng/mL, anycurable 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 knownhypersensitivity to a control arm regimen may still be eligible if they have nohypersensitivity to other potential control arm IMPs.
  15. Serious medical or psychiatric illness likely to interfere with participation in thisclinical study
  16. Recent cancer treatment (chemotherapy, immunotherapy, biological therapy) within 4weeks of starting trial treatment; systemic steroid treatment (prednisolone > 10mgdaily (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 ICTregimen 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 inflammatoryheart disease for ICT regimen containing doxorubicin, or severe heart failure (NewYork Heart Association Class IV) or severe, uncontrolled cardiac disease for ICTregimen containing rituximab

Study Design

Total Participants: 284
Treatment Group(s): 11
Primary Treatment: Vincristine
Phase: 2
Study Start date:
September 04, 2023
Estimated Completion Date:
November 30, 2031

Study 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).

Connect with a study center

  • NHS Grampian

    Aberdeen,
    United Kingdom

    Site Not Available

  • Belfast Health & Social Care Trust

    Belfast,
    United Kingdom

    Site Not Available

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham,
    United Kingdom

    Site Not Available

  • Blackpool Teaching Hospitals NHS Foundation Trust

    Blackpool,
    United Kingdom

    Site Not Available

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge,
    United Kingdom

    Site Not Available

  • Cardiff and vale University LHB

    Cardiff,
    United Kingdom

    Site Not Available

  • University Hospitals Coventry and Warwickshire NHS Trust

    Coventry,
    United Kingdom

    Site Not Available

  • Croydon Health Services NHS Trust

    Croydon,
    United Kingdom

    Site Not Available

  • NHS Greater Glasgow and Clyde

    Glasgow,
    United Kingdom

    Site Not Available

  • The Leeds Teaching Hospitals NHS Trust

    Leeds,
    United Kingdom

    Site Not Available

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Liverpool,
    United Kingdom

    Site Not Available

  • Guy's and St Thomas' NHS Foundation Trust

    London,
    United Kingdom

    Site Not Available

  • King's College Hospital NHS Foundation Trust

    London,
    United Kingdom

    Site Not Available

  • The Royal Marsden NHS Foundation Trust

    London,
    United Kingdom

    Site Not Available

  • University College London Hospital NHS Foundation Trust

    London,
    United Kingdom

    Site Not Available

  • The Christie NHS Foundation Trust

    Manchester,
    United Kingdom

    Active - Recruiting

  • The Newcastle Upon Tyne Hospitals NHS Foundation Trust

    Newcastle,
    United Kingdom

    Site Not Available

  • Norfolk and Norwich University Hospitals NHS Foundation Trust

    Norwich,
    United Kingdom

    Site Not Available

  • Nottingham University Hospitals NHS Trust

    Nottingham,
    United Kingdom

    Active - Recruiting

  • Oxford University Hospitals NHS Foundation Trust

    Oxford,
    United Kingdom

    Site Not Available

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield,
    United Kingdom

    Site Not Available

  • University Hospital Southampton NHS Foundation Trust

    Southampton,
    United Kingdom

    Site Not Available

  • University Hospital of North Midlands NHS Trust

    Stoke-on-Trent,
    United Kingdom

    Site Not Available

  • Swansea Bay University Local Health Board

    Swansea,
    United Kingdom

    Site Not Available

  • Torbay and South Devon NHS Foundation Trust

    Torquay,
    United Kingdom

    Site Not Available

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