A Trial Looking at Rituximab and Chemotherapy as a Treatment for Follicular Lymphoma in Elderly Patients

NCT ID: NCT01303887

Last Updated: 2025-04-18

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

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

680 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2023-05-11

Brief Summary

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The purpose of this study is to determine whether R-FC is more beneficial that R-CVP in the treatment of older patients (aged 60 or over) with Follicular Lymphoma (FL).

Detailed Description

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FL predominantly affects the elderly, yet the optimum treatment for older patients with the disease has not been defined. The present study aims to address this question by comparing the drug combination that is currently considered the gold-standard (R-CVP) with a newer combination (R-FC) that might be more effective without being significantly more toxic. In order to take into account the balance between efficacy and toxicity, a dual primary endpoint has been employed: progression-free survival and toxicity in the form of grade 3-4 infection.

Conditions

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Follicular Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Study Groups

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R-CVP

Repeated every 21 days for up to 8 cycles with response assessment after 4 cycles. Responders (PR/CR) after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

Rituximab 375mg/m2 IV day 1,repeated every 21 days for 8 cycles. All patients who have achieved a CR or PR to induction therapy will receive rituximab maintenance (375mg/m2 every 2 months for 2 years).

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)

Vincristine

Intervention Type DRUG

Vincristine 1.4mg/m2 IV day 1,repeated every 21 days for 8 cycles.

Prednisolone

Intervention Type DRUG

Prednisolone 40mg/m2 PO day 1-5, repeated every 21 days for 8 cycles.

R-FC

Repeated every 21 days for 4 cycles. Responders (PR/CR) after 4 cycles will receive 4 further cycles of Rituximab only. Responders after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)

Fludarabine

Intervention Type DRUG

Fludarabine 40mg/m2 PO day 1-3,repeated every 21 days for 4 cycles

Interventions

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Rituximab

Rituximab 375mg/m2 IV day 1,repeated every 21 days for 8 cycles. All patients who have achieved a CR or PR to induction therapy will receive rituximab maintenance (375mg/m2 every 2 months for 2 years).

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)

Intervention Type DRUG

Vincristine

Vincristine 1.4mg/m2 IV day 1,repeated every 21 days for 8 cycles.

Intervention Type DRUG

Prednisolone

Prednisolone 40mg/m2 PO day 1-5, repeated every 21 days for 8 cycles.

Intervention Type DRUG

Fludarabine

Fludarabine 40mg/m2 PO day 1-3,repeated every 21 days for 4 cycles

Intervention Type DRUG

Other Intervention Names

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Mabthera Cyclophosphamide monohydrate vincristine sulfate Deltacortril Fludara

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed follicular lymphoma (grade 1,2, and 3a with material available for central review)
* Ann Arbor stage II-IV
* Aged 60 years or over, or aged less than 60 but anthracycline-based therapy contra-indicated
* No prior systemic therapy (one episode of prior local radiotherapy is allowed)
* At least one of the following criteria for initiation of treatment:
* Rapid generalized disease progression in the preceding 3 months
* Life threatening organ involvement
* Renal or macroscopic liver infiltration
* Bone lesions
* Presence of systemic symptoms or pruritus
* Haemoglobin \< 10 g/dL or WBC \< 3.0 × 109/L or platelet counts \< 100 × 109/L due to marrow involvement
* Adequate haematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow):
* Haemoglobin ≥ 8.0 g/dL
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Written Informed Consent

Exclusion Criteria

* Overt transformation to diffuse large B-cell lymphoma
* Grade 3b follicular lymphoma
* Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis)
* WHO performance status 3 or 4
* Impaired renal function defined as estimated Glomerular filtration rate (eGFR) \< 30 mL/min using the Modification of Diet in Renal Disease (MDRD) formula
* Impaired hepatic function defined as serum bilirubin more than twice upper limit of normal (unless due to lymphoma or Gilbert's syndrome)
* Life expectancy less than 12 months
* Pre-existing neuropathy
* Active auto-immune haemolytic anaemia
* Serological evidence of infection with HIV, hepatitis B (positivity for surface antigen or core antibody) or hepatitis C
* Allergy to murine proteins
* Corticosteroid treatment during the last 4 weeks, unless administered at a dose equivalent to no more than prednisolone 20mg/day continuously or a single course of prednisolone 1 mg/kg for up to 7 days
* Concomitant malignancies except adequately treated localised non-melanoma skin cancer or adequately treated in situ cervical cancer, or cancers that have been in remission for at least 5 years following surgery with curative intent.
* Major surgery (excluding lymph node biopsy) within 28 days prior to randomisation
* Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease)
* Treatment within a clinical trial within 30 days prior to trial entry
* Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent
* Adult patient under tutelage (not competent to sign informed consent)
* Pregnant or lactating women
* All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Liverpool University Hospitals NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

Cancer Research UK

OTHER

Sponsor Role collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

University of Liverpool

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Pettitt, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Liverpool and Royal Liverpool and Broadgreen University Hospitals Trust

Locations

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Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

Ysbyty Gwynedd

Bangor, , United Kingdom

Site Status

Birmingham Heartlands

Birmingham, , United Kingdom

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Royal Bournemouth Hospital

Bournemouth, , United Kingdom

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Bradford Royal Infirmary

Bradford, , United Kingdom

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Frenchay Hospital

Bristol, , United Kingdom

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Queen's Hospital, Burton

Burton-on-Trent, , United Kingdom

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Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, , United Kingdom

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Velindre Hospital

Cardiff, , United Kingdom

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Countess of Chester

Chester, , United Kingdom

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Leighton Hospital

Crewe, , United Kingdom

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Trafford General Hospital

Davyhulme, , United Kingdom

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Russels Hall Hospital

Dudley, , United Kingdom

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Royal Devon & Exeter Hospital

Exeter, , United Kingdom

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Falkirk & District Royal Infirmary

Falkirk, , United Kingdom

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Queen Elizabeth Hospital

Gateshead, , United Kingdom

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Medway Maritime Hospital

Gillingham, , United Kingdom

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Beatson Oncology Centre

Glasgow, , United Kingdom

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Royal Alexandra Hospital

Glasgow, , United Kingdom

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Harrogate District Foundation Trust

Harrogate, , United Kingdom

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Northwick Park Hospital

Harrow, , United Kingdom

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Princess Royal Hospital, Bromley

Hayes, , United Kingdom

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Huddersfield Royal Infirmary

Huddersfield, , United Kingdom

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Castle Hill Hospital

Hull, , United Kingdom

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Raigmore Hospital,

Inverness, , United Kingdom

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Ipswich Hospital

Ipswich, , United Kingdom

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Kettering General Hospital

Kettering, , United Kingdom

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The Queen Elizabeth Hospital, Kings Lynn

Kings Lynn, , United Kingdom

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St James University Hospital

Leeds, , United Kingdom

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Leicester Royal Infirmary

Leicester, , United Kingdom

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Royal Liverpool University Hospital

Liverpool, , United Kingdom

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University Hospital Aintree

Liverpool, , United Kingdom

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Guys & St Thomas Hospital

London, , United Kingdom

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Kings College Hospital

London, , United Kingdom

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Royal Free Hospital

London, , United Kingdom

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St Bartholomews Hospital

London, , United Kingdom

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University College Hospital

London, , United Kingdom

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Altnagelvin Hospital

Londonderry, , United Kingdom

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Luton & Dunstable Hospital

Luton, , United Kingdom

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Kent Oncology Centre

Maidstone, , United Kingdom

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Manchester Royal Infirmary

Manchester, , United Kingdom

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The Christie Hospital

Manchester, , United Kingdom

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Arrowe Park Hospital

Metropolitan Borough of Wirral, , United Kingdom

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Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

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Northampton General Hospital

Northampton, , United Kingdom

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Mount Vernon Hospital

Northwood, , United Kingdom

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Nottingham City Hospital

Nottingham, , United Kingdom

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Derriford Hospital

Plymouth, , United Kingdom

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Whiston Hospital

Prescot, , United Kingdom

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Queens Hospital

Romford, , United Kingdom

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Salford Royal Hospital

Salford, , United Kingdom

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Salisbury District Hospital

Salisbury, , United Kingdom

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Diana Princess of Wales Hospital

Scunthorpe, , United Kingdom

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Royal Hallamshire Hospital

Sheffield, , United Kingdom

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Wexham Park Hospital

Slough, , United Kingdom

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South Tyneside District General Hospital

South Shields, , United Kingdom

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Basingstoke and North Hampshire Hospital

Southampton, , United Kingdom

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Southampton General Hospital

Southampton, , United Kingdom

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St Richards Hospital

Southampton, , United Kingdom

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Glan Clwyd Hospital

St Asaph, , United Kingdom

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Stafford District General Hospital

Stafford, , United Kingdom

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Lister Hospital

Stevenage, , United Kingdom

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Sunderland Royal Hospital

Sunderland, , United Kingdom

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Great Western Hospital

Swindon, , United Kingdom

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Torbay District General Hospital

Torquay, , United Kingdom

Site Status

Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Hillingdon Hospital

Uxbridge, , United Kingdom

Site Status

Pinderfields General Hospital

Wakefield, , United Kingdom

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West Herts

Watford, , United Kingdom

Site Status

Worcestershire Acute Hospitals NHS Trust

Worcester, , United Kingdom

Site Status

Worthing Hospital

Worthing, , United Kingdom

Site Status

York District Hospital

York, , United Kingdom

Site Status

Countries

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United Kingdom

Related Links

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Other Identifiers

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2008-004759-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN99217456

Identifier Type: -

Identifier Source: org_study_id

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