PACIFICO

Title

Purine-Alkylator Combination In Follicular lymphoma Immuno-Chemotherapy for Older patients

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
III	Treatment	Open	Over 60	University of Liverpool and RLBUHT	EUDRACT No: 2008-004759-31 ISRCTN No:

Trial Description

Purpose

Follicular lymphoma (FL) is the most frequently occurring type of indolent non-Hodgkin's lymphoma (NHL) in developed countries. The annual incidence is highest in patients aged 60 or over (1). The disease is usually widespread at presentation and is not curable with currently available treatments. The clinical course is one of recurrent remissions and relapses, the median survival being approximately 10 years from diagnosis

In the UK, R-CVP is approved by NICE for the first-line treatment of FL and is consequently regarded as the standard induction regimen for patients of all ages.

Older patients are almost certainly under-represented in clinical trials of FL owing to a trend for treatment regimens to become ever more intensive and because of the increasing stringency of inclusion criteria. Consequently, there is a lack of data concerning the optimal R-chemotherapy induction regimen in this patient group. The present study aims to remedy this situation by targeting patients with FL aged 60 or over.

Eligibility

Stage II-IV FL (histological grade 1, 2, and 3a) requiring first-line treatment by conventional criteria
Aged 60 years or over (or less than 60 but more intensive chemotherapy considered inappropriate due to co-morbidity)

Treatment/Intervention

To compare R-FC and R-CVP in older patients with symptomatic advanced-stage FL for response rates, progression-free survival (primary end-point), overall survival, toxicity (primary end-point), quality of life and cost effectiveness. Translational studies will also be performed, aiming to identify biomarkers that predict therapeutic response and outcome

This study is a two arm, open-label, multi-centre, parallel group, phase III, randomised controlled trial comparing R-FC and R-CVP in older patients with symptomatic advanced-stage FL for response rates, progression-free survival (primary end-point), overall survival, toxicity (primary end-point), quality of life and cost effectiveness.

Translational studies will also be performed, aiming to identify biomarkers that predict therapeutic response and outcome.

Patients will be randomised equally between the two arms:

R-CVP (Rituximab, Cyclophosphamide, Vincristine, Prednisolone)
R-FC (Rituximab, Fludarabine, Cyclophosphamide)

Responders will receive 2 years of rituximab maintenance. All patients will be followed up for at least 3 years.

Trial Endpoints

Primary Outcome

Progression free survival
Toxicity

Secondary outcomes

Response rates (overall, complete and partial) following initial therapy
Response rates following maintenance therapy
Overall survival
Number of treatment cycles delivered
Cumulative dose of individual drugs administered
Quality of life (EORTC QLQ-30 (v3) and EQ-5D)
Cost effectiveness
Response to second-line therapy

Trial Lead Organisations

The Royal Liverpool and Broadgreen University Hospital Trust
University of Liverpool
Chief Investigator: Professor Andrew Pettitt

Trial Sites

There are now 37 sites open in the trial:

Aberdeen Royal Infirmary, Aberdeen (Dr. Dominic Culligan)
Addenbrookes Hospital, Cambridge (Dr. George Follows)
Arrowe Park Hospital, Upton (Dr. Ranjit K Dasgupta)
Basingstoke and North Hampshire Hospital, Southampton (Dr. Alison Milne)
Bradford Royal Infirmary, Bradford (Dr. Lisa Newton)
Countess of Chester Hospital, Chester (Dr. Salaheddin Tueger)
Derriford Hospital, Plymouth (Dr. Simon Rule)
Frenchay Hospital, Bristol (Dr. Sophie Otton)
Great Western Hospital, Swindon (Dr. Norbert Blesing)
Hillingdon Hospital, Uxbridge (Dr. Richard Kaczmarski)
Kent and Canterbury Hospital, Canterbury (Dr. Christopher Pocock)
Kent Oncology Centre, Maidstone (Dr. Saad Rassam)
Manchester Royal Infirmary, Manchester (Dr. Kate Ryan)
Mount Vernon Hospital, Northwood (Dr. Kirit Ardeshna)
Northwick Park Hospital, Harrow (Dr. Charalampia Kyriakou)
Nottingham City Hospital, Nottingham (Dr. Andrew McMillan)
Queen's Hospital, Burton, Burton-upon-Trent (Dr. Humayun Ahmad)
Queens Hospital, Romford, Romford (Dr. Alison Brownell)
Raigmore Hospital, Inverness (Dr Peter Forsyth)
Royal Cornwall Hospital (Treliske), Truro (Dr. Anton Kruger)
Royal Devon & Exeter Hospital, Exeter (Dr. Anthony Todd)
Royal Liverpool University Hospital, Liverpool (Prof. Andrew Pettitt)
Russels Hall Hospital, Dudley (Dr. Savio Fernandes)
Salford Royal Hospital, Salford (Dr. Simon Jowitt)
Southampton General Hospital, Southampton (Prof. Peter Johnson)
St Bartholomews Hospital, London (Dr. Silvia Montoto)
St James University Hospital, Leeds (Dr. Rod Johnson)
St Richards Hospital, Southampton (Dr. Philip Bevan)
Stafford District General Hospital, Stafford (Dr. Paul Revell)
Sunderland Royal Hospital, Sunderland (Dr. Simon Lyons)
The Christie, Manchester (Prof. John Radford)
Torbay District General Hospital, Torquay (Dr. Deborah Turner)
University College Hospital, London (Dr. Kirit Ardeshna)
University Hospital Aintree, Bebington (Dr. Barrie Woodcock)
Whiston Hospital, Prescot (Dr. James A T Nicholson)
Worthing Hospital, Worthing (Dr. Santhosh Narat)
York District Hospital, York (Dr. Laura Munro)

The following sites have expressed an interest:

Altnagelvin Hospital, Londonderry (Dr. Feargal McNicholl)
Barnet General Hospital, Enfield (Dr. Andres Virchis)
Beatson Oncology Centre, Glasgow (Dr. Pam McKay)
Belfast City Hospital, Belfast (Dr. Paul Kettle)
Birmingham Heartlands, Birmingham (Prof Don Milligan)
Blackpool Victoria, Blackpool (Dr. Marian Macheta)
Castle Hill Hospital, Hull (Dr. Russell Patmore)
Cheltenham General Hospital, Cheltenham (Dr. Kim Benstead)
Churchill Hospital, Oxford (Dr. Chris Hatton)
Conquest Hospital, Eastbourne (Dr. Judy Beard)
Crosshouse Hospital, Kilmarnock (Dr. Julie Gillies)
Darent Valley Hospital, Dartford (Dr. Tariq Shafi)
Diana Princess of Wales Hospital, Scunthorpe (Dr. Hanna Ciepluch)
Essex County Hospital, Colchester (Dr. Mike Hamblin)
Falkirk & District Royal Infirmary, Falkirk (Dr. Marie Hughes)
George Eliot Hospital, Nuneaton (Dr. Mekkali Narayanan)
Glan Clwyd Hospital, St Asaph (Dr. Christine Hoyle)
Guys & St Thomas Hospital, London (Dr. Paul Fields)
Harrogate District Foundation Trust, Harrogate (Dr. Claire J. Hall)
Hemel Hempstead General, Northwood (Dr. Justin Harrison)
Huddersfield Royal Infirmary, Huddersfield (Dr Sylvia Feyler)
Ipswich Hospital, Ipswich (Dr. Jamie Morgan)
James Paget Hospital, Great Yarmouth (Dr. Shalal Sadullah)
Kettering General Hospital, Kettering (Dr Matthew Lyttelton)
Kings College Hospital, London (Dr. Robert Marcus)
Leicester Royal Infirmary, Leicester (Dr. Ben Kennedy)
Leighton Hospital, Crewe (Dr Kamaraj Karunanithi)
Lincoln County Hospital, Lincoln (Dr. Gabriel Anghel)
Lister Hospital, Stevenage (Dr Judith Hanslip)
Luton & Dunstable Hospital, Luton (Prof. Peter Hoskin)
Mayday Hospital, Croydon (Dr. Nnenna Osuji)
Medway Hospital, Gillingham (Dr. M. Aldouri)
Monklands Hospital, Airdrie (Dr. Iain Singer)
Ninewells Hospital, Dundee (Dr. David Meiklejohn)
Norfolk and Norwich University Hospital, Norwich (Dr. Kris Bowles)
Northampton General Hospital, Northampton (Dr Angela Bowen)
Pinderfields General Hospital, Wakefield (Dr Paul Moreton)
Princess Royal Hospital, Bromley, Hayes (Dr. Anil K Lakhani)
Queen Elizabeth Hospital, Gateshead, Gateshead (Dr. Scott Marshall)
Queen Elizabeth Hospital, Kings Lynn, King's Lynn (Dr. Natasha Curtin)
Research and Development Department, Stoke-on-Trent (Dr. Richard Chasty)
Royal Alexandra Hospital, Glasgow (Dr. Alison Sefcick)
Royal Berkshire Hospital, Reading (Dr. Stuart Mucklow)
Royal Bournemouth Hospital, Bournemouth (Dr Helen McCarthy)
Royal Derby Hospital, Derby (Dr Adrian Smith)
Royal Free Hospital, London (Dr. Christopher McNamara)
Royal Hallamshire Hospital, Sheffield (Dr. Josh Wright)
Royal Marsden Hospital, Sutton (Prof. David Cunningham)
Royal Preston Hospital, Preston (Dr Maqsood Punekar)
Royal Sussex County Hospital, Brighton (Dr. Andrew Webb)
Royal Victoria Infirmary, Newcastle upon Tyne (Dr. Anne Lennard)
Sandwell Hospital, Birmingham (Dr Yasmin Hasan)
Singleton Hospital, Swansea (Dr. Saad Al-Ismail)
South Tyneside District General Hospital, South Shields (Dr. Simon Lyons)
St Georges Hospital, London, London (Dr. Ruth Pettengell)
St Helier Hospital, Carshalton (Dr. Jane Mercieca)
St Mary's Hospital, London, London (Dr Sasha Marks)
Trafford General Hospital, Davyhulme (Dr. Patrick Carrington)
University Hospital of Wales, Cardiff (Dr. Clare Rowntree)
University Hospitals Coventry, Coventry (Dr. Beth Harrison)
Velindre Hospital, Cardiff (Dr. Eve Gallop-Evans)
Warrington Hospital, Warrington (Dr. Mohamed Kaleel Rahman)
Warwick Hospital, Warwick (Dr. Anton Borg)
West Suffolk Hospital, Bury St. Edmunds (Dr. Mamatha Karanth)
Western General Hospital, Edinburgh (Dr. Fiona Scott)
Weston General Hospital, Weston-Super-Mare (Dr Agata Wrzesien-Kus)
Wexham Park Hospital, Slough (Dr Simon Moule)
Worcester Royal Infirmary, Worcester (Dr. Salim Shafeek)
Wythenshawe Hospital, Manchester (Dr Simon Watt)
Ysbyty Gwynedd, Bangor (Dr. David Edwards)

Registry Information

Official Title