Trial Title:
Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy
NCT ID:
NCT05848765
Condition:
Relapsed Follicular Lymphoma
Refractory Follicular Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Prednisone
Cyclophosphamide
Bendamustine Hydrochloride
Rituximab
Doxorubicin
Vincristine
Lenalidomide
Obinutuzumab
Conditions: Keywords:
Epcoritamab
Lymphoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Epcoritamab
Description:
Bispecific antibody
Arm group label:
Round 1: Epcoritamab and lenalidomide
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Immunomodulatory agent
Arm group label:
All rounds: Investigator Choice Therapy
Arm group label:
Round 1: Epcoritamab and lenalidomide
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Monoclonal antibody
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
Monoclonal antibody
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Bendamustine
Description:
Alkylating agent (chemotherapy drug)
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Antineoplastic, Vinca Alkaloid
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
Anthracycline
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Alkylating agent (chemotherapy drug)
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Prednisone
Description:
Corticosteroid
Arm group label:
All rounds: Investigator Choice Therapy
Intervention type:
Drug
Intervention name:
Investigation agent 2
Description:
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
Arm group label:
Round 2
Intervention type:
Drug
Intervention name:
Investigation agent 3
Description:
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
Arm group label:
Round 3
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.
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).
Criteria for eligibility:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
NHS Grampian
Address:
City:
Aberdeen
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Belfast Health & Social Care Trust
Address:
City:
Belfast
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
University Hospitals Birmingham NHS Foundation Trust
Address:
City:
Birmingham
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Blackpool Teaching Hospitals NHS Foundation Trust
Address:
City:
Blackpool
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Cambridge University Hospitals NHS Foundation Trust
Address:
City:
Cambridge
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Cardiff and vale University LHB
Address:
City:
Cardiff
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
University Hospitals Coventry and Warwickshire NHS Trust
Address:
City:
Coventry
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Croydon Health Services NHS Trust
Address:
City:
Croydon
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
NHS Greater Glasgow and Clyde
Address:
City:
Glasgow
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
The Leeds Teaching Hospitals NHS Trust
Address:
City:
Leeds
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
The Clatterbridge Cancer Centre NHS Foundation Trust
Address:
City:
Liverpool
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Guy's and St Thomas' NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
King's College Hospital NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
University College London Hospital NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Address:
City:
Newcastle
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Norfolk and Norwich University Hospitals NHS Foundation Trust
Address:
City:
Norwich
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Nottingham University Hospitals NHS Trust
Address:
City:
Nottingham
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Oxford University Hospitals NHS Foundation Trust
Address:
City:
Oxford
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Sheffield Teaching Hospitals NHS Foundation Trust
Address:
City:
Sheffield
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
University Hospital Southampton NHS Foundation Trust
Address:
City:
Southampton
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
University Hospital of North Midlands NHS Trust
Address:
City:
Stoke-on-Trent
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Swansea Bay University Local Health Board
Address:
City:
Swansea
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Torbay and South Devon NHS Foundation Trust
Address:
City:
Torquay
Country:
United Kingdom
Status:
Not yet recruiting
Start date:
September 4, 2023
Completion date:
November 30, 2031
Lead sponsor:
Agency:
University of Birmingham
Agency class:
Other
Collaborator:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
Genmab
Agency class:
Industry
Source:
University of Birmingham
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05848765
