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

Follicular Lymphoma Clinical Trial

— PACIFICO  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01303887
• Other study ID #: ISRCTN99217456
• Secondary ID: 2008-004759-31
• Status: Recruiting
• Phase: Phase 3
• First received: February 24, 2011
• Last updated: May 4, 2011
• Start date: October 2009
• Est. completion date: September 2016

Study information

• Verified date: October 2010
• Source: University of Liverpool
• Contact: Kathryn Marley
• Phone: +44 (0)151 794 8897
• Email: kathryn.marley[@]liverpool.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 680
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

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).
• Cyclophosphamide
Cyclophosphamide 250mg/m2 PO day 1-3, repeated every 21 days for 4 (R-FC) or 8 cycles (R-CVP)
• Vincristine
Vincristine 1.4mg/m2 IV day 1,repeated every 21 days for 8 cycles.
• Prednisolone
Prednisolone 40mg/m2 PO day 1-5, repeated every 21 days for 8 cycles.
• Fludarabine
Fludarabine 40mg/m2 PO day 1-3,repeated every 21 days for 4 cycles

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Ysbyty Gwynedd	Bangor
United Kingdom	Birmingham Heartlands	Birmingham
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	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	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	Altnagelvin Hospital	Londonderry
United Kingdom	Luton & Dunstable Hospital	Luton
United Kingdom	Kent Oncology Centre	Maidstone
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	Hillingdon Hospital	Uxbridge
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

Sponsors (4)

Lead Sponsor	Collaborator
University of Liverpool	Cancer Research UK, Roche Pharma AG, Royal Liverpool and Broadgreen University Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity	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	Yes
Primary	Progression-free survival		30 months	No
Secondary	Response rates (overall, complete and partial) following initial therapy		24 weeks	No
Secondary	Response rates following maintenance therapy		30 months	No
Secondary	Response duration		30 months	Yes
Secondary	Overall survival		End of study	No
Secondary	Time to next treatment		End of study	No
Secondary	Rate of large cell transformation		End of study	No
Secondary	Response to second-line therapy		30 months	No
Secondary	Number of treatment cycles delivered		30 months	No
Secondary	Cumulative dose of individual drugs administered		30 months	No
Secondary	Quality of life		End of study	No
Secondary	Cost effectiveness		End of study	No

External Links

•   Cancer Research UK
•   UKCRN