Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05848765
Other study ID # RG_22-020
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date September 4, 2023
Est. completion date November 30, 2031

Study information

Verified date November 2023
Source University of Birmingham
Contact Trial Coordinator
Phone 0121 371 7861
Email refract@trials.bham.ac.uk
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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).


Recruitment information / eligibility

Status Recruiting
Enrollment 284
Est. completion date November 30, 2031
Est. primary completion date May 31, 2029
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
Epcoritamab
Bispecific antibody
Lenalidomide
Immunomodulatory agent
Rituximab
Monoclonal antibody
Obinutuzumab
Monoclonal antibody
Bendamustine
Alkylating agent (chemotherapy drug)
Vincristine
Antineoplastic, Vinca Alkaloid
Doxorubicin
Anthracycline
Cyclophosphamide
Alkylating agent (chemotherapy drug)
Prednisone
Corticosteroid
Investigation agent 2
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 3
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

Locations

Country Name City State
United Kingdom NHS Grampian Aberdeen
United Kingdom Belfast Health & Social Care Trust Belfast
United Kingdom University Hospitals Birmingham NHS Foundation Trust Birmingham
United Kingdom Blackpool Teaching Hospitals NHS Foundation Trust Blackpool
United Kingdom Cambridge University Hospitals NHS Foundation Trust Cambridge
United Kingdom Cardiff and vale University LHB Cardiff
United Kingdom University Hospitals Coventry and Warwickshire NHS Trust Coventry
United Kingdom Croydon Health Services NHS Trust Croydon
United Kingdom NHS Greater Glasgow and Clyde Glasgow
United Kingdom The Leeds Teaching Hospitals NHS Trust Leeds
United Kingdom The Clatterbridge Cancer Centre NHS Foundation Trust Liverpool
United Kingdom Guy's and St Thomas' NHS Foundation Trust London
United Kingdom King's College Hospital NHS Foundation Trust London
United Kingdom The Royal Marsden NHS Foundation Trust London
United Kingdom University College London Hospital NHS Foundation Trust London
United Kingdom The Christie NHS Foundation Trust Manchester
United Kingdom The Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle
United Kingdom Norfolk and Norwich University Hospitals NHS Foundation Trust Norwich
United Kingdom Nottingham University Hospitals NHS Trust Nottingham
United Kingdom Oxford University Hospitals NHS Foundation Trust Oxford
United Kingdom Sheffield Teaching Hospitals NHS Foundation Trust Sheffield
United Kingdom University Hospital Southampton NHS Foundation Trust Southampton
United Kingdom University Hospital of North Midlands NHS Trust Stoke-on-Trent
United Kingdom Swansea Bay University Local Health Board Swansea
United Kingdom Torbay and South Devon NHS Foundation Trust Torquay

Sponsors (3)

Lead Sponsor Collaborator
University of Birmingham Cancer Research UK, Genmab

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 24 weeks
Secondary 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 24 weeks
Secondary 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 10 years
Secondary 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 10 years
Secondary 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 10 years
Secondary 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 10 years
Secondary 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 10 years
Secondary 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 Collected from start of treatment until 60 days after treatment
Secondary Quality of Life (QoL) Measured using the EQ-5D-5L and FACT-Lym 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)
Secondary Quality of Life (QoL) Measured using the FACT-Lym 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)
See also
  Status Clinical Trial Phase
Withdrawn NCT04635683 - Lenalidomide, Umbralisib, and Ublituximab for the Treatment of Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma Phase 1
Active, not recruiting NCT01955499 - Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma Phase 1
Not yet recruiting NCT06068881 - A Study to Assess Efficacy and Safety of Oral Tazemetostat in Adult Participants With Relapsed/Refractory Follicular Lymphoma That Does Not Have an "EZH2 Gain-of-function" Genetic Mutation Phase 2
Active, not recruiting NCT03583424 - Venetoclax, Carmustine, Etoposide, Cytarabine, and Melphalan Before Stem Cell Transplant in Treating Participants With Relapsed or Refractory Non-Hodgkin Lymphoma Phase 1/Phase 2
Recruiting NCT04007029 - Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia Phase 1
Withdrawn NCT03579927 - CAR.CD19-CD28-zeta-2A-iCasp9-IL15-Transduced Cord Blood NK Cells, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Participants With B-cell Lymphoma Phase 1/Phase 2
Active, not recruiting NCT04578600 - CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma Phase 1
Recruiting NCT04447716 - An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment Phase 1
Recruiting NCT05025800 - ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma Phase 1/Phase 2
Completed NCT03019640 - Umbilical Cord Blood NK Cells, Rituximab, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma Phase 2
Completed NCT02927964 - TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma Phase 1/Phase 2
Terminated NCT04699461 - Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma Phase 2
Completed NCT02869633 - Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant Phase 2
Active, not recruiting NCT02568553 - Lenalidomide and Blinatumomab for the Treatment of Relapsed Non-Hodgkin Lymphoma Phase 1
Completed NCT01995669 - Lenalidomide and Obinutuzumab in Treating Patients With Relapsed Indolent Non-Hodgkin Lymphoma Phase 1/Phase 2
Withdrawn NCT05152459 - Tazemetostat in Combination With Umbralisib and Ublituximab for the Treatment Relapsed or Refractory Follicular Lymphoma Phase 1/Phase 2
Active, not recruiting NCT03401853 - Pembrolizumab With Rituximab or Obinutuzumab in Treating Patients With Relapsed or Refractory Follicular Lymphoma or Diffuse Large B Cell Lymphoma Phase 2
Active, not recruiting NCT03479268 - Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory CLL or Non-Hodgkin Lymphoma Phase 1
Recruiting NCT06191887 - B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells With Fludarabine and Cyclophosphamide Lymphodepletion for the Treatment of Relapsed or Refractory B-cell Hematologic Malignancies Phase 1
Active, not recruiting NCT02956382 - Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma Phase 1/Phase 2