A Trial Looking at Rituximab and Chemotherapy as a Treatment for Follicular Lymphoma in Elderly Patients
- Conditions
- Follicular Lymphoma
- Interventions
- Registration Number
- NCT01303887
- Lead Sponsor
- University of Liverpool
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 680
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R-CVP Rituximab 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). R-CVP Cyclophosphamide 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). R-CVP Vincristine 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). R-CVP Prednisolone 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). R-FC Cyclophosphamide 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). R-FC Fludarabine 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).
- Primary Outcome Measures
Name Time Method Toxicity 36 months The second primary outcome measure is grade 3-4 infection occurring anytime from the start of treatment until 6 months following the last dose of treatment, and this will be used as the toxicity end-point. Toxicity will be measured according to standard National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 following each cycle of treatment and at each subsequent follow-up visit until 6 months following the last dose of treatment.
Progression-free survival 30 months
- Secondary Outcome Measures
Name Time Method Response rates (overall, complete and partial) following initial therapy 24 weeks Response rates following maintenance therapy 30 months Response duration 30 months Overall survival End of study Time to next treatment End of study Rate of large cell transformation End of study Response to second-line therapy 30 months Number of treatment cycles delivered 30 months Cumulative dose of individual drugs administered 30 months Quality of life End of study Cost effectiveness End of study
Trial Locations
- Locations (73)
Ysbyty Gwynedd
🇬🇧Bangor, United Kingdom
Birmingham Heartlands
🇬🇧Birmingham, United Kingdom
Luton & Dunstable Hospital
🇬🇧Luton, United Kingdom
Kent Oncology Centre
🇬🇧Maidstone, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, United Kingdom
Frenchay Hospital
🇬🇧Bristol, United Kingdom
Queen's Hospital, Burton
🇬🇧Burton-upon-Trent, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
Velindre Hospital
🇬🇧Cardiff, United Kingdom
Countess of Chester
🇬🇧Chester, United Kingdom
Leighton Hospital
🇬🇧Crewe, United Kingdom
Trafford General Hospital
🇬🇧Davyhulme, United Kingdom
Russels Hall Hospital
🇬🇧Dudley, United Kingdom
Hillingdon Hospital
🇬🇧Uxbridge, United Kingdom
Royal Devon & Exeter Hospital
🇬🇧Exeter, United Kingdom
Falkirk & District Royal Infirmary
🇬🇧Falkirk, United Kingdom
Queen Elizabeth Hospital
🇬🇧Gateshead, United Kingdom
Medway Maritime Hospital
🇬🇧Gillingham, United Kingdom
Beatson Oncology Centre
🇬🇧Glasgow, United Kingdom
Royal Alexandra Hospital
🇬🇧Glasgow, United Kingdom
Harrogate District Foundation Trust
🇬🇧Harrogate, United Kingdom
Northwick Park Hospital
🇬🇧Harrow, United Kingdom
Princess Royal Hospital, Bromley
🇬🇧Hayes, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, United Kingdom
Castle Hill Hospital
🇬🇧Hull, United Kingdom
Raigmore Hospital,
🇬🇧Inverness, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, United Kingdom
Kettering General Hospital
🇬🇧Kettering, United Kingdom
The Queen Elizabeth Hospital, Kings Lynn
🇬🇧Kings Lynn, United Kingdom
St James University Hospital
🇬🇧Leeds, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom
University Hospital Aintree
🇬🇧Liverpool, United Kingdom
Altnagelvin Hospital
🇬🇧Londonderry, United Kingdom
Guys & St Thomas Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
St Bartholomews Hospital
🇬🇧London, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
The Christie Hospital
🇬🇧Manchester, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Northampton General Hospital
🇬🇧Northampton, United Kingdom
Mount Vernon Hospital
🇬🇧Northwood, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Whiston Hospital
🇬🇧Prescot, United Kingdom
Queens Hospital
🇬🇧Romford, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Salisbury District Hospital
🇬🇧Salisbury, United Kingdom
Diana Princess of Wales Hospital
🇬🇧Scunthorpe, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Wexham Park Hospital
🇬🇧Slough, United Kingdom
South Tyneside District General Hospital
🇬🇧South Shields, United Kingdom
Basingstoke and North Hampshire Hospital
🇬🇧Southampton, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
St Richards Hospital
🇬🇧Southampton, United Kingdom
Glan Clwyd Hospital
🇬🇧St Asaph, United Kingdom
Stafford District General Hospital
🇬🇧Stafford, United Kingdom
Lister Hospital
🇬🇧Stevenage, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, United Kingdom
Great Western Hospital
🇬🇧Swindon, United Kingdom
Torbay District General Hospital
🇬🇧Torquay, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Pinderfields General Hospital
🇬🇧Wakefield, United Kingdom
West Herts
🇬🇧Watford, United Kingdom
Arrowe Park Hospital
🇬🇧Wirral, United Kingdom
Worcestershire Acute Hospitals NHS Trust
🇬🇧Worcester, United Kingdom
Worthing Hospital
🇬🇧Worthing, United Kingdom
York District Hospital
🇬🇧York, United Kingdom