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

This study is currently recruiting participants.
Verified October 2010 by University of Liverpool
Sponsor:
Collaborators:
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Cancer Research UK
Roche Pharma AG
Information provided by:
University of Liverpool
ClinicalTrials.gov Identifier:
NCT01303887
First received: February 24, 2011
Last updated: May 4, 2011
Last verified: October 2010
  Purpose

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).


Condition Intervention Phase
Follicular Lymphoma
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Prednisolone
Drug: Fludarabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Liverpool:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rates (overall, complete and partial) following initial therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Response rates following maintenance therapy [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Response duration [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Time to next treatment [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Rate of large cell transformation [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Response to second-line therapy [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Number of treatment cycles delivered [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Cumulative dose of individual drugs administered [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Cost effectiveness [ Time Frame: End of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 680
Study Start Date: October 2009
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Mabthera
Drug: Cyclophosphamide
Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)
Other Name: Cyclophosphamide monohydrate
Drug: Vincristine
Vincristine 1.4mg/m2 IV day 1,repeated every 21 days for 8 cycles.
Other Name: vincristine sulfate
Drug: Prednisolone
Prednisolone 40mg/m2 PO day 1-5, repeated every 21 days for 8 cycles.
Other Name: 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 Name: Cyclophosphamide monohydrate
Drug: Fludarabine
Fludarabine 40mg/m2 PO day 1-3,repeated every 21 days for 4 cycles
Other Name: Fludara

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

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01303887

Contacts
Contact: Kathryn Marley +44 (0)151 794 8897 kathryn.marley@liverpool.ac.uk
Contact: James Dodd +44 (0)151 795 5288 jpdodd@liverpool.ac.uk

  Show 73 Study Locations
Sponsors and Collaborators
University of Liverpool
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Cancer Research UK
Roche Pharma AG
Investigators
Principal Investigator: Andrew Pettitt, Professor University of Liverpool and Royal Liverpool and Broadgreen University Hospitals Trust
  More Information

Additional Information:
UKCRN  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Professor Andrew Pettitt, University of Liverpool
ClinicalTrials.gov Identifier: NCT01303887     History of Changes
Other Study ID Numbers: ISRCTN99217456, 2008-004759-31
Study First Received: February 24, 2011
Last Updated: May 4, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Liverpool:
PACIFICO
Follicular Lymphoma
Non-Hodgkin's Lymphoma
Rituximab
R-CVP
R-FC
Older

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Fludarabine
Prednisolone
Methylprednisolone Hemisuccinate
Vincristine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 20, 2014