Clinical trial NCT01303887: A Trial Looking at Rituximab and Chemotherapy as a Treatment for Follicular Lymphoma in Elderly Patients
Official title: Purine-Alkylator Combination In Follicular Lymphoma Immuno-Chemotherapy for Older Patients: a Phase III Comparison of First-line R-CVP Versus R-FC
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Follicular Lymphoma
Keywords: PACIFICO
Follicular Lymphoma
Non-Hodgkin's Lymphoma
Rituximab
R-CVP
R-FC
Older
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Liverpool University Hospitals NHS Foundation Trust
name: Cancer Research UK
name: Roche Pharma AG
First posted: 2011-02-25
Enrollment: 680
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Toxicity
timeFrame: 36 months
measure: Progression-free survival
timeFrame: 30 months
Secondary outcomes:
measure: Response rates (overall, complete and partial) following initial therapy
timeFrame: 24 weeks
measure: Response rates following maintenance therapy
timeFrame: 30 months
measure: Response duration
timeFrame: 30 months
measure: Overall survival
timeFrame: End of study
measure: Time to next treatment
timeFrame: End of study
measure: Rate of large cell transformation
timeFrame: End of study
measure: Response to second-line therapy
timeFrame: 30 months
measure: Number of treatment cycles delivered
timeFrame: 30 months
measure: Cumulative dose of individual drugs administered
timeFrame: 30 months
measure: Quality of life
timeFrame: End of study
measure: Cost effectiveness
timeFrame: End of study
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Bristol
country: United Kingdom
facility: Frenchay Hospital
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital, Burton
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Chester
country: United Kingdom
facility: Countess of Chester
city: Crewe
country: United Kingdom
facility: Leighton Hospital
city: Davyhulme
country: United Kingdom
facility: Trafford General Hospital
city: Dudley
country: United Kingdom
facility: Russels Hall Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
city: Falkirk
country: United Kingdom
facility: Falkirk & District Royal Infirmary
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
city: Glasgow
country: United Kingdom
facility: Royal Alexandra Hospital
city: Harrogate
country: United Kingdom
facility: Harrogate District Foundation Trust
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
city: Hayes
country: United Kingdom
facility: Princess Royal Hospital, Bromley
city: Huddersfield
country: United Kingdom
facility: Huddersfield Royal Infirmary
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Inverness
country: United Kingdom
facility: Raigmore Hospital,
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Kettering
country: United Kingdom
facility: Kettering General Hospital
city: Kings Lynn
country: United Kingdom
facility: The Queen Elizabeth Hospital, Kings Lynn
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: Londonderry
country: United Kingdom
facility: Altnagelvin Hospital
city: London
country: United Kingdom
facility: Guys & St Thomas Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St Bartholomews Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Luton
country: United Kingdom
facility: Luton & Dunstable Hospital
city: Maidstone
country: United Kingdom
facility: Kent Oncology Centre
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Prescot
country: United Kingdom
facility: Whiston Hospital
city: Romford
country: United Kingdom
facility: Queens Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
city: Scunthorpe
country: United Kingdom
facility: Diana Princess of Wales Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Slough
country: United Kingdom
facility: Wexham Park Hospital
city: South Shields
country: United Kingdom
facility: South Tyneside District General Hospital
city: Southampton
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Southampton
country: United Kingdom
facility: St Richards Hospital
city: St Asaph
country: United Kingdom
facility: Glan Clwyd Hospital
city: Stafford
country: United Kingdom
facility: Stafford District General Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
city: Swindon
country: United Kingdom
facility: Great Western Hospital
city: Torquay
country: United Kingdom
facility: Torbay District General Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital
city: Watford
country: United Kingdom
facility: West Herts
city: Wirral
country: United Kingdom
facility: Arrowe Park Hospital
city: Worcester
country: United Kingdom
facility: Worcestershire Acute Hospitals NHS Trust
city: Worthing
country: United Kingdom
facility: Worthing Hospital
city: York
country: United Kingdom
facility: York District Hospital
Study officials:
affiliation: University of Liverpool and Royal Liverpool and Broadgreen University Hospitals Trust
name: Andrew Pettitt, Professor
role: PRINCIPAL_INVESTIGATOR
References: