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

April 16, 2025 updated by: University of Liverpool

Purine-Alkylator Combination In Follicular Lymphoma Immuno-Chemotherapy for Older Patients: a Phase III Comparison of First-line R-CVP Versus R-FC

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

680

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Aberdeen, United Kingdom
        • Aberdeen Royal Infirmary
      • Bangor, United Kingdom
        • Ysbyty Gwynedd
      • Birmingham, United Kingdom
        • Birmingham Heartlands
      • Bournemouth, United Kingdom
        • Royal Bournemouth Hospital
      • Bradford, United Kingdom
        • Bradford Royal Infirmary
      • Bristol, United Kingdom
        • Frenchay Hospital
      • Burton-upon-Trent, United Kingdom
        • Queen's Hospital, Burton
      • Cambridge, United Kingdom
        • Addenbrookes Hospital
      • Canterbury, United Kingdom
        • Kent and Canterbury Hospital
      • Cardiff, United Kingdom
        • Velindre Hospital
      • Chester, United Kingdom
        • Countess of Chester
      • Crewe, United Kingdom
        • Leighton Hospital
      • Davyhulme, United Kingdom
        • Trafford General Hospital
      • Dudley, United Kingdom
        • Russels Hall Hospital
      • Exeter, United Kingdom
        • Royal Devon & Exeter Hospital
      • Falkirk, United Kingdom
        • Falkirk & District Royal Infirmary
      • Gateshead, United Kingdom
        • Queen Elizabeth Hospital
      • Gillingham, United Kingdom
        • Medway Maritime Hospital
      • Glasgow, United Kingdom
        • Beatson Oncology Centre
      • Glasgow, United Kingdom
        • Royal Alexandra Hospital
      • Harrogate, United Kingdom
        • Harrogate District Foundation Trust
      • Harrow, United Kingdom
        • Northwick Park Hospital
      • Hayes, United Kingdom
        • Princess Royal Hospital, Bromley
      • Huddersfield, United Kingdom
        • Huddersfield Royal Infirmary
      • Hull, United Kingdom
        • Castle Hill Hospital
      • Inverness, United Kingdom
        • Raigmore Hospital,
      • Ipswich, United Kingdom
        • Ipswich Hospital
      • Kettering, United Kingdom
        • Kettering General Hospital
      • Kings Lynn, United Kingdom
        • The Queen Elizabeth Hospital, Kings Lynn
      • Leeds, United Kingdom
        • St James University Hospital
      • Leicester, United Kingdom
        • Leicester Royal Infirmary
      • Liverpool, United Kingdom
        • Royal Liverpool University Hospital
      • Liverpool, United Kingdom
        • University Hospital Aintree
      • London, United Kingdom
        • Kings College Hospital
      • London, United Kingdom
        • Royal Free Hospital
      • London, United Kingdom
        • University College Hospital
      • London, United Kingdom
        • Guys & St Thomas Hospital
      • London, United Kingdom
        • St Bartholomews Hospital
      • Londonderry, United Kingdom
        • Altnagelvin Hospital
      • Luton, United Kingdom
        • Luton & Dunstable Hospital
      • Maidstone, United Kingdom
        • Kent Oncology Centre
      • Manchester, United Kingdom
        • Manchester Royal Infirmary
      • Manchester, United Kingdom
        • The Christie Hospital
      • Newcastle upon Tyne, United Kingdom
        • Royal Victoria Infirmary
      • Northampton, United Kingdom
        • Northampton General Hospital
      • Northwood, United Kingdom
        • Mount Vernon Hospital
      • Nottingham, United Kingdom
        • Nottingham City Hospital
      • Plymouth, United Kingdom
        • Derriford Hospital
      • Prescot, United Kingdom
        • Whiston Hospital
      • Romford, United Kingdom
        • Queens Hospital
      • Salford, United Kingdom
        • Salford Royal Hospital
      • Salisbury, United Kingdom
        • Salisbury District Hospital
      • Scunthorpe, United Kingdom
        • Diana Princess of Wales Hospital
      • Sheffield, United Kingdom
        • Royal Hallamshire Hospital
      • Slough, United Kingdom
        • Wexham Park Hospital
      • South Shields, United Kingdom
        • South Tyneside District General Hospital
      • Southampton, United Kingdom
        • Southampton General Hospital
      • Southampton, United Kingdom
        • Basingstoke and North Hampshire Hospital
      • Southampton, United Kingdom
        • St Richards Hospital
      • St Asaph, United Kingdom
        • Glan Clwyd Hospital
      • Stafford, United Kingdom
        • Stafford District General Hospital
      • Stevenage, United Kingdom
        • Lister Hospital
      • Sunderland, United Kingdom
        • Sunderland Royal Hospital
      • Swindon, United Kingdom
        • Great Western Hospital
      • Torquay, United Kingdom
        • Torbay District General Hospital
      • Truro, United Kingdom
        • Royal Cornwall Hospital
      • Uxbridge, United Kingdom
        • Hillingdon Hospital
      • Wakefield, United Kingdom
        • Pinderfields General Hospital
      • Watford, United Kingdom
        • West Herts
      • Wirral, United Kingdom
        • Arrowe Park Hospital
      • Worcester, United Kingdom
        • Worcestershire Acute Hospitals NHS Trust
      • Worthing, United Kingdom
        • Worthing Hospital
      • York, United Kingdom
        • York District Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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).
Drug: 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).
Other Names:
  • Mabthera
Drug: Cyclophosphamide
Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)
Other Names:
  • Cyclophosphamide monohydrate
Drug: Vincristine
Vincristine 1.4mg/m2 IV day 1,repeated every 21 days for 8 cycles.
Other Names:
  • vincristine sulfate
Drug: Prednisolone
Prednisolone 40mg/m2 PO day 1-5, repeated every 21 days for 8 cycles.
Other Names:
  • Deltacortril
Experimental: 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).
Drug: Cyclophosphamide
Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)
Other Names:
  • Cyclophosphamide monohydrate
Drug: Fludarabine
Fludarabine 40mg/m2 PO day 1-3,repeated every 21 days for 4 cycles
Other Names:
  • Fludara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 30 months
30 months
Toxicity
Time Frame: 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.
36 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: End of study
End of study
Response rates (overall, complete and partial) following initial therapy
Time Frame: 24 weeks
24 weeks
Response rates following maintenance therapy
Time Frame: 30 months
30 months
Response duration
Time Frame: 30 months
30 months
Time to next treatment
Time Frame: End of study
End of study
Rate of large cell transformation
Time Frame: End of study
End of study
Response to second-line therapy
Time Frame: 30 months
30 months
Number of treatment cycles delivered
Time Frame: 30 months
30 months
Cumulative dose of individual drugs administered
Time Frame: 30 months
30 months
Quality of life
Time Frame: End of study
End of study
Cost effectiveness
Time Frame: End of study
End of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Liverpool

Collaborators

Roche Pharma AG
Cancer Research UK
Liverpool University Hospitals NHS Foundation Trust

Investigators

  • Principal Investigator: Andrew Pettitt, Professor, University of Liverpool and Royal Liverpool and Broadgreen University Hospitals Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2009

Primary Completion (Actual)

May 11, 2023

Study Completion (Actual)

May 11, 2023

Study Registration Dates

First Submitted

February 24, 2011

First Submitted That Met QC Criteria

February 24, 2011

First Posted (Estimated)

February 25, 2011

Study Record Updates

Last Update Posted (Actual)

April 18, 2025

Last Update Submitted That Met QC Criteria

April 16, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISRCTN99217456
  • 2008-004759-31 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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