Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

284 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-04

Study Completion Date

2031-11-30

Brief Summary

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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

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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).

Conditions

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Relapsed Follicular Lymphoma Refractory Follicular Lymphoma

Keywords

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Epcoritamab Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Round 1: Epcoritamab and lenalidomide

Epcoritamab (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.

Group Type EXPERIMENTAL

Epcoritamab

Intervention Type DRUG

Bispecific antibody

Lenalidomide

Intervention Type DRUG

Immunomodulatory agent

Round 2

Investigation agent 2

Group Type EXPERIMENTAL

Investigation agent 2

Intervention Type DRUG

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

Round 3

Investigation agent 3

Group Type EXPERIMENTAL

Investigation agent 3

Intervention Type DRUG

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

All rounds: Investigator Choice Therapy

Choice 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.

Group Type ACTIVE_COMPARATOR

Lenalidomide

Intervention Type DRUG

Immunomodulatory agent

Rituximab

Intervention Type DRUG

Monoclonal antibody

Obinutuzumab

Intervention Type DRUG

Monoclonal antibody

Bendamustine

Intervention Type DRUG

Alkylating agent (chemotherapy drug)

Vincristine

Intervention Type DRUG

Antineoplastic, Vinca Alkaloid

Doxorubicin

Intervention Type DRUG

Anthracycline

Cyclophosphamide

Intervention Type DRUG

Alkylating agent (chemotherapy drug)

Prednisone

Intervention Type DRUG

Corticosteroid

Interventions

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Epcoritamab

Bispecific antibody

Intervention Type DRUG

Lenalidomide

Immunomodulatory agent

Intervention Type DRUG

Rituximab

Monoclonal antibody

Intervention Type DRUG

Obinutuzumab

Monoclonal antibody

Intervention Type DRUG

Bendamustine

Alkylating agent (chemotherapy drug)

Intervention Type DRUG

Vincristine

Antineoplastic, Vinca Alkaloid

Intervention Type DRUG

Doxorubicin

Anthracycline

Intervention Type DRUG

Cyclophosphamide

Alkylating agent (chemotherapy drug)

Intervention Type DRUG

Prednisone

Corticosteroid

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Locations

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