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

ISRCTN	ISRCTN99217456
DOI	https://doi.org/10.1186/ISRCTN99217456
EudraCT/CTIS number	2008-004759-31
ClinicalTrials.gov number	NCT01303887
Secondary identifying numbers	N/A

Submission date: 22/01/2009
Registration date: 03/03/2009
Last edited: 20/03/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/trials-search/trial-looking-rituximab-chemotherapy-treatment-follicular-lymphoma-elderly-patients-pacifico

Study website

Contact information

Prof Andrew Pettitt
Scientific

University of Liverpool School of Cancer Studies
Division of Haematology
Level 2 Duncan Building
Royal Liverpool University Hospital
Daulby Street
Liverpool
L69 3GA
United Kingdom

Phone	+44 (0)151 706 4363
Email	arp@liv.ac.uk

Study information

Study design	Phase III randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Purine-alkylator combination in follicular lymphoma immuno-chemotherapy for older patients: a phase III randomised controlled trial
Study acronym	PACIFICO
Study objectives	To investigate if the new immuno-chemotherapy combination regimen rituximab, fludarabine and cyclophosphamide (R-FC) improves rate of progression-free survival in older patients (aged 60+ years) when compared to the current gold standard treatment of rituximab, cyclophosphamide, vincristine and prednisone (R-CVP), without being significantly more toxic. Patients aged less than 60 years will be considered for the trial if more intensive chemotherapy is considered inappropriate due to co-morbidity.
Ethics approval(s)	Added 09/03/2010: 1. Liverpool Adult Research Ethics Committee (MREC), 19/06/2009, ref: 09/H1005/29 2. Medicines and Healthcare products Regulatory Agency (MHRA), 03/07/2009, ref: 04196/0014/001-0001
Health condition(s) or problem(s) studied	Follicular lymphoma
Intervention	Control arm (R-CVP): Rituximab 375 mg/m^2 intravenous (IV) day 1, cyclophosphamide 750 mg/m^2 IV day 1, vincristine 1.4 mg/m^2 IV day 1, prednisolone 40 mg/m^2 orally (PO) day 1 - 5, repeated every 21 days for 8 cycles. Experimental arm (R-FC): Rituximab 375 mg/m^2 IV day 1, fludarabine 40 mg/m^2 PO day 1 - 3, cyclophosphamide 250 mg/m^2 PO day 1 - 3, repeated every 21 days for 4 cycles followed by rituximab 375 mg/m^2 alone for 4 further cycles. Rituximab maintenance: All patients who have achieved a complete response (CR) or partial response (PR) to induction therapy will receive rituximab maintenance (375 mg/m^2 every 2 months for 2 years).
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Rituximab, fludarabine, cyclophosphamide, vincristine, prednisone
Primary outcome measure	1. Progression free survival (PFS): length of PFS defined as number of days between date of randomisation and the date of progression, date of death from any cause or the date last seen progression free (censor date) 2. Toxicity: grade 3 - 4 infection 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.
Secondary outcome measures	1. Response rates (overall, complete and partial) following initial therapy - assessment made following initial therapy 2. Response rates following maintenance therapy - assessment made following maintenance therapy 3. Response duration - time to event outcome 4. Overall survival - time to event outcome 5. Time to treatment failure - time to event outcome 6. Time-to-next treatment - time to event outcome 7. Number of treatment cycles delivered - assessment made following second-line therapy 8. Cumulative dose of individual drugs administered - assessment made following initial therapy 9. Quality of life - EORTC QLQ C-30, EQ-5D and EQ-VAS questionnaires will be completed at various time points during the course of treatment and follow up 10. Cost effectiveness - will be assessed at various time points during the course of treatment and follow up 11. Response to second-line therapy - assessment made following second-line therapy
Overall study start date	01/05/2009
Completion date	01/07/2019

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	680
Key inclusion criteria	1. Histologically confirmed follicular lymphoma, grade 1, 2, and 3a with material available for central review 2. Ann Arbor stage II - IV, i.e. all patients except those with strictly localised disease for whom local radiotherapy would be appropriate. Lymph nodes should be considered pathologically enlarged if the long axis is more than 1.5 cm regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is more than 1.0 cm. 3. Aged 60 years or over (or less than 60 but more intensive chemotherapy considered inappropriate due to co-morbidity), either sex 4. At least one of the following British National Lymphoma Investigation (BNLI) criteria for initiation of treatment: 4.1. Rapid generalised disease progression in the preceding 3 months 4.2. Life threatening organ involvement 4.3. Renal of macroscopic liver infiltration 4.4. Bone lesions 4.5. Presence of systemic symptoms or pruritus 4.6. Haemoglobin less than 10 g/dL or whole blood cell count (WBC) less than 3.0 × 10^9/L or platelet count less than 100 × 10^9/L due to marrow involvement 5. Adequate haematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to registration: 5.1. Haemoglobin greater than or equal to 8.0 g/dL 5.2. Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L 5.3. Platelet count greater than or equal to 100 x 10^9/L 6. Written informed consent
Key exclusion criteria	1. Prior anti-lymphoma treatment 2. Overt transformation to diffuse large B-cell lymphoma 3. World Health Organization (WHO) performance status 3 or 4 4. Creatinine clearance less than 30 ml/min 5. Serum bilirubin more than twice upper limit of normal (unless due to lymphoma) 6. Life expectancy less than 12 months 7. Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C. Patients with any serological evidence of current or past exposure to HIV, hepatitis B or hepatitis C are excluded unless the serological findings are clearly due to vaccination. 8. Allergy to murine proteins 9. Grade 3b follicular lymphoma 10. Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis) 11. Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to less than 20 mg/day prednisolone 12. Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer 13. Major surgery (excluding lymph node biopsy) within 28 days prior to registration 14. 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) 15. Treatment within a clinical trial within 30 days prior to trial entry 16. Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent 17. Adult patient under tutelage (not competent to sign informed consent)
Date of first enrolment	01/05/2009
Date of final enrolment	01/05/2017

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University of Liverpool School of Cancer Studies

Liverpool
L69 3GA
United Kingdom

Sponsor information

University of Liverpool (UK)
University/education

Research and Business Services
The Foresight Centre
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom

Website	http://www.liv.ac.uk/
"ROR"	https://ror.org/04xs57h96

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK) (ref: C18029/A10015)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

20/03/2020: EudraCT number added.
10/10/2018: The overall trial end date was changed from 01/05/2017 to 01/07/2019.
09/03/2010: The ethics approval details for this trial were added. This information can be found in the ethics approval field.