Condition category
Cancer
Date applied
08/08/2014
Date assigned
08/08/2014
Last edited
10/09/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Mr Jamie Oughton

ORCID ID

Contact details

Clinical Trials Research Unit (CTRU)
Woodhouse Lane
Leeds
LS2 9JT
United Kingdom
+44 (0)113 343 1494
j.oughton@leeds.ac.uk

Additional identifiers

EudraCT number

2013-001944-76

ClinicalTrials.gov number

Protocol/serial number

16675

Study information

Scientific title

FLAIR: Front-Line therapy in CLL: Assessment of Ibrutinib-containing Regimes: a randomised controlled trial

Acronym

FLAIR

Study hypothesis

Current hypothesis as of 07/09/2018:
The trial originally aimed to compare the effect on progression-free survival (PFS) of ibrutinib plus rituximab (IR) with that of fludarabine, cyclophosphamide and rituximab (FCR) in patients with previously untreated chronic lymphocytic leukaemia (CLL).

The amendment to include the additional trial arms will allow a comparison of PFS between ibrutinib plus venetoclax (I+V) and ibrutinib alone (I) with FCR, and a comparison of minimal residual disease (MRD) negativity rates in I+V with those in I.

Previous hypothesis:
The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of progression-free survival.

Ethics approval

NRES Committee Yorkshire & The Humber - Leeds West, 17/06/2014, ref: 14/YH/0085

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: Cancer; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)

Intervention

Current interventions as of 07/09/2018:
Participants will be randomised on a 1:1:1 basis to receive standard therapy with fludarabine, cyclophosphamide and rituximab (FCR), ibrutinib monotherapy (I) or ibrutinib + venetoclax (I+V).

The IR arm has been closed to recruitment.

Previous interventions as of 29/06/2017:
Participants will be randomised on a 1:1:1:1 basis to receive standard therapy with fludarabine, cyclophosphamide and rituximab (FCR), ibrutinib plus rituximab (IR), ibrutinib monotherapy (I) or ibrutinib + venetoclax (I+V).

Added 24/07/2017:
FCR: fludarabine (oral), cyclophosphamide (oral) and rituximab (intravenous infusion). F (24mg/m2/day) and C (150mg/m2/day) are administered days 1-5 and R is administered at 375mg/ m2 for day 1 cycle 1 and then at 500mg/m2 for day 1 for cycles 2-6. Each cycle is repeated every 28 days and there are 6 cycles.
IR: ibrutinib (oral) and rituximab. 6 cycles of R as per FCR. Ibrutinib (420mg) is administered daily for six years.
I: ibrutinib monotherapy is administered as per IR
I+V: ibrutinib + venetoclax (oral): ibrutinib is administered as per IR. Venetoclax is given daily from week 9 onwards in weekly dose increments (20mg, 50mg, 100mg, 200mg and 400mg) after which 400mg is administered for six years.
Follow up: baseline, 9 months post randomisation then every six months until 7 years or disease progression. All participants will be followed up at least annually until death.

Previous interventions:
Participants will be randomised on a 1:1 basis to receive standard therapy with fludarabine, cyclophosphamide and rituximab (FCR) or ibrutinib plus rituximab (IR).

Intervention type

Drug

Phase

Not Applicable

Drug names

Fludarabine, cyclophosphamide, rituximab, ibrutinib, venetoclax

Primary outcome measure

Current primary outcome measure as of 07/09/2018:
1. Whether I+V is superior to FCR in terms of progression-free survival.
2. Whether I+V is superior to I in terms of Minimal Residual Disease negativity. The proportion of concurrently randomised participants who are MRD negative in the bone marrow at any time during the trial will be summarised by treatment arm and compared using a binary logistic regression model adjusted for the minimisation factors and trial stage, excluding centre, and Kaplan-Meier curves will be presented. The analysis of MRD negativity will be initially carried out at 2 years after the close of recruitment.

Previous primary outcome measure:
The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of progression-free survival, and whether IR toxicity rates are favourable.

Secondary outcome measures

Current secondary outcome measures as of 10/09/2018:
1. PFS of I+V in comparison with I. This is assessed using time from randomisation to first documented evidence of disease progression (as defined by IWCLL criteria) or death from any cause. Participants who do not progress will be censored at the last date they were known to be alive and progression-free.
2. PFS of I in comparison with FCR. This is assessed using time from randomisation to first documented evidence of disease progression (as defined by IWCLL criteria) or death from any cause. Participants who do not progress will be censored at the last date they were known to be alive and progression free.
3. Overall survival. This is assessed using time from randomisation to date of death from any cause. Participants not known to have died will be censored at the date they were last known to be alive.
4. Proportion of participants obtaining undetectable MRD, as defined by IWCLL criteria. A negative MRD is defined as the presence of <0.01% CLL cells in the bone marrow. Achievement of MRD negativity is defined as a MRD negative results at any time over the length of the trial.
5. Stopping I-containing therapy in MRD negative patients. Participants receiving I, IR or I+V who achieve MRD negativity in the bone marrow will be able to stop treatment. MRD levels will be monitored over time following stopping treatment.
6. Restarting I-containing therapy on MRD relapse. Those who relapse at the MRD level will restart treatment and will be assessed further for MRD response.
7. Response to therapy, as defined by IWCLL criteria. For participants randomised to FCR or IR, response is assessed at 3 months post-treatment with FCR or R and again at the end of treatment with ibrutinib for participants randomised to IR. For participants randomised to I or I+V, response is assessed at 9 months post-randomisation and again at the end of treatment.
8. Safety and toxicity assessed using adverse events reported throughout the trial, as graded by CTCAE V4.03 , and determined by routine clinical assessments at each centre.
9. Health-related quality of life. The EORTC QLQC30 and EORTC QLQCLL16 will be used to measure participant assessed QoL prior to randomisation, at the end of treatment with FCR and R (for participants randomised to FCR or IR) or at 6 months post-randomisation (for participants randomised to I or I+V), and then at 6-monthly visits.
10. Cost-effectiveness. The SF12 and EQ5D will be used to produce quality adjusted life years (QALYs). NHS resource use and participants’ out of pocket expenses will be collected via the Case Record Forms, as well as health economics patient questionnaires. These will be collected prior to randomisation, at the end of treatment with FCR and R (for participants randomised to FCR or IR) or at 6 months post-randomisation (for participants randomised to I or I+V), and then at 6-monthly visits.

Previous secondary outcome measures as of 07/09/2018:
1. PFS of I+V in comparison with I
2. PFS of I in comparison with FCR
3. Overall survival
4. Proportion of participants obtaining undetectable MRD, as defined by IWCLL criteria
5. Stopping of I-containing therapy in MRD-negative patients. Participants who have an MRD negative result in the peripheral blood at any timepoint between 12 and 30 months post-randomisation will be eligible to stop treatment prior to the 6 years post-randomisation timepoint if they confirm MRD negativity in the bone marrow.
6. Time to MRD relapse for participants who stop I-containing treatment based on MRD negativity and then go on to relapse at the MRD
7. Response to therapy, as defined by IWCLL criteria. For each comparison, the best response for each participant at either 3 months post-treatment with FCR, 9 months post randomisation (for participants randomised to I or I+V) or the end of treatment (for I or I+V) will be summarised by treatment group and overall. The proportion of participants achieving a Complete Response (CR+CRi) and an Overall Response (at least a PR) at any stage during the trial will be summarised by treatment arm
8. Safety and toxicity. Safety analyses will summarise the AR, SAE, SAR and SUSAR rates per participant, by treatment received and overall for all participants randomised to stages II and III. ARs will be presented by CTCAE toxicity grade (V4.0.3).
9. Health-related quality of life assessed using all domains of the EORTC QLQ-C30 and the CLL-specific module, EORTC QLQ-CLL16.
10. Cost-effectiveness

Previous secondary outcome measures:
1. Overall survival
2. Undetectable minimal residual disease
3. Response to therapy
4. Health-related quality of life
5. Cost-effectiveness

Overall trial start date

01/08/2014

Overall trial end date

01/01/2030

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. At least 18 years old. Maximum age of 75 years old.
2. B-CLL with a characteristic immunophenotype, including small lymphocytic lymphoma
3. Binet’s Stages C, B or Progressive Stage A
4. Requiring therapy by the IWCLL criteria in that they must have at least one of the following:
4.1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.
4.2. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
4.3. Massive nodes (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
4.4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months as long as the lymphocyte count is over 30 x 10^9/L
4.5. A minimum of any one of the following disease-related symptoms must be present:
4.5.1. Unintentional weight loss more than or equal to 10% within the previous 6 months.
4.5.2. Significant fatigue (i.e. Eastern Cooperative Oncology Group PS 2 or worse; cannot work or unable to perform usual activities)
4.5.3. Fevers of greater than 38.0°C for 2 or more weeks without other evidence of infection
4.5.4. Night sweats for more than 1 month without evidence of infection
5. Considered fit for treatment with FCR as determined by the treating clinician
6. World Health Organisation (WHO) performance status (PS) of 0, 1 or 2
7. Able to provide written informed consent
8. Biochemical values must be within the following limits within 14 days prior to randomization and at baseline:
8.1. Alanine aminotransferase (ALT) 3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) 3 x ULN.
8.2. Total bilirubin = 1.5 x ULN, unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1576; UK Sample Size: 1576

Participant exclusion criteria

Current exclusion criteria as of 07/09/2018:
1. Prior therapy for CLL
2. History or current evidence of Richter’s transformation
3. Major surgery within 4 weeks prior to randomisation
4. Active infection
5. Above 20% P53 deletion, determined by FISH
6. Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies
7. Concomitant warfarin or equivalent vitamin K inhibitor - added 29/06/2017: or other oral anticoagulant treatment; anyone requiring anticoagulation treatment for greater than 6 months is not eligible for trial entry
8. Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment with rituximab has finished, or 30 days after treatment with ibrutinib has finished, whichever is latest. Women must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction
9. Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment with rituximab has finished, or 3 months after treatment with ibrutinib has finished, whichever is latest, unless they are surgically sterile
10. CNS involvement with CLL
11. Symptomatic cardiac failure not controlled by therapy, or unstable angina not adequately controlled by current therapy (in patients with a significant cardiac history the left ventricular function should be assessed and patients with severe impairment should be excluded)
12. Respiratory impairment (bronchiectasis or moderate COPD)
13. Other severe, concurrent diseases or mental disorders that could interfere with their ability to participate in the study
14. Inability to swallow oral medication
15. Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease etc)
16. Known HIV positive
17. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded
18. Positive serology for Hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result
19. History of prior malignancy, with the exception of the following:
19.1. Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
19.2. Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
19.3. Adequately treated cervical carcinoma in situ without current evidence of disease
20. Persisting severe pancytopenia (neutrophils <0.5 x 10^9/l or platelets <50 x 10^9/l) unless due to direct marrow infiltration by CLL
21. Current treatment with prednisolone of >10 mg/day
22. Active haemolysis (patients with haemolysis controlled with prednisolone at a dose 10 mg or less per day can be entered into the trial)
23. Patients with a creatinine clearance of less than 30 ml/min (either measured or derived by the Cockcroft Gault formula or alternative locally approved formula)
24. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
25. Requirement for treatment with a strong CYP3A4/5 inhibitor or inducer
26. Cardiac event (eg. recent myocardial infarction, coronary artery stent) requiring dual antiplatelet treatment.
27. Allergy or inability to tolerate uric acid reducing agents (eg allopurinol/rasburicase).
28. Unwilling or unable to take PCP prophylaxis (eg cotrimoxazole).

Previous exclusion criteria:
1. Prior therapy for CLL
2. History or current evidence of Richter’s transformation
3. Major surgery within 4 weeks prior to randomisation
4. Active infection
5. Above 20% P53 deletion, determined by FISH
6. Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies
7. Concomitant warfarin or equivalent vitamin K inhibitor - added 29/06/2017: or other oral anticoagulant treatment; anyone requiring anticoagulation treatment for greater than 6 months is not eligible for trial entry
8. Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment with rituximab has finished, or 30 days after treatment with ibrutinib has finished, whichever is latest. Women must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction
9. Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment with rituximab has finished, or 3 months after treatment with ibrutinib has finished, whichever is latest, unless they are surgically sterile
10. CNS involvement with CLL
11. Symptomatic cardiac failure not controlled by therapy, or unstable angina not adequately controlled by current therapy (in patients with a significant cardiac history the left ventricular function should be assessed and patients with severe impairment should be excluded)
12. Respiratory impairment (bronchiectasis or moderate COPD)
13. Other severe, concurrent diseases or mental disorders that could interfere with their ability to participate in the study
14. Inability to swallow oral medication
15. Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease etc)
16. Known HIV positive
17. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded
18. Positive serology for Hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result
19. History of prior malignancy, with the exception of the following:
19.1. Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
19.2. Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
19.3. Adequately treated cervical carcinoma in situ without current evidence of disease
20. Persisting severe pancytopenia (neutrophils <0.5 x 10^9/l or platelets <50 x 10^9/l) unless due to direct marrow infiltration by CLL
21. Current treatment with prednisolone of >10 mg/day
22. Active haemolysis (patients with haemolysis controlled with prednisolone at a dose 10 mg or less per day can be entered into the trial)
23. Patients with a creatinine clearance of less than 30 ml/min (either measured or derived by the Cockcroft Gault formula or alternative locally approved formula)
24. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
25. Requirement for treatment with a strong CYP3A4/5 inhibitor or inducer

Recruitment start date

01/09/2014

Recruitment end date

01/01/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Trials Research Unit (CTRU)
Leeds
LS2 9JT
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Foresterhill Road
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Altnagelvin Hospital
WHSCT Glenshane Road Glenshane
Londonderry
BT47 6SB
United Kingdom

Trial participating centre

Barnet General Hospital
Wellhouse Lane Hertfordshire
Barnet
EN5 3DJ
United Kingdom

Trial participating centre

Colchester General Hospital
Department of Haematology Colchester General Hospital Turner Road Colchester Essex
Colchester
CO4 5JL
United Kingdom

Trial participating centre

Basingstoke and North Hampshire Hospital
Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom

Trial participating centre

Royal Hampshire County Hospital
Romsey Road
Winchester
SO22 5DG
United Kingdom

Trial participating centre

Beatson Oncology Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Victoria Hospital, Glasgow
52 Grange Road
Glasgow
G42 9LF
United Kingdom

Trial participating centre

Royal Alexandra Hospital
Corsebar Road
Paisley
PA2 9PN
United Kingdom

Trial participating centre

Belfast City Hospital
Belfast Health and Social Care Trust 51 Lisburn Road
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Birmingham Heartlands Hospital
Birmingham
B9 5SS
United Kingdom

Trial participating centre

Good Hope Hospital
Rectory Road
Sutton Coldfield
B75 7RR
United Kingdom

Trial participating centre

Blackpool Victoria Hospital
Whinney Heys Road Lancashire
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

Borders General Hospital
Melrose
TD6 9BS
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Bradford Teaching Hospitals NHS Foundation Trust Duckworth Lane West Yorkshire BD9 6RJ
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Trial participating centre

Calderdale Royal Hospital
Salterhebble
Halifax
HX3 0PW
United Kingdom

Trial participating centre

Huddersfield Royal Infirmary
Acre Street Lindley
Huddersfield
HD3 3EA
United Kingdom

Trial participating centre

Castle Hill Hospital
Castle Road
Cottingham
HU16 5JQ
United Kingdom

Trial participating centre

Gloucestershire Royal Hospital
Great Western Road
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

Cheltenham General Hospital
Sandford Road
Cheltenham
GL53 7AN
United Kingdom

Trial participating centre

Christie Hospital
Christie NHS Foundation Trust Wilmslow Road
Manchester
M20 4BX
United Kingdom

Trial participating centre

Churchill Hospital
Oxford Cancer Centre & Cancer Research UK Oxford University Hospitals NHS Trust
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Basildon Hospital
Basildon
SS16 5NL
United Kingdom

Trial participating centre

Countess of Chester Hospital
Chester
CH2 1UL
United Kingdom

Trial participating centre

Craigavon Area Hospital
68 Lurgan Road
Portadown
BT63 5QQ
United Kingdom

Trial participating centre

Croydon University Hospital
530 London Road
Croydon
CR7 7YE
United Kingdom

Trial participating centre

Derriford Hospital
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

East Surrey Hospital
Canada Avenue Redhill Surrey
Redhill
RH1 5RH
United Kingdom

Trial participating centre

Epsom General Hospital
Dorking Road
Epsom
KT18 7EG
United Kingdom

Trial participating centre

St Helier Hospital
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom

Trial participating centre

George Eliot Hospital
College Street
Nuneaton
CV10 7DJ
United Kingdom

Trial participating centre

Glan Clwyd Hospital
Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom

Trial participating centre

Lincoln County Hospital
Haematology Department Lincoln County Hospital Greetwell Road Lincoln Lincolnshire (E Mid)
Lincoln
LN2 5QY
United Kingdom

Trial participating centre

Grantham & District Hospital
Manthorpe Road
Grantham
NG31 8DG
United Kingdom

Trial participating centre

Pilgrim Hospital
Sibsey Road
Boston
PE21 9QS
United Kingdom

Trial participating centre

Harrogate District Hospital
Lancaster Park Road
Harrogate
HG2 7SX
United Kingdom

Trial participating centre

Hammersmith Hospital
Imperial College Healthcare NHS Trust Du Cane Road
London
W12 0HS
United Kingdom

Trial participating centre

Ipswich Hospital
Ipswich Hospital NHS Trust Heath Road Suffolk
Ipswich
IP4 5PD
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

James Paget Hospital
Great Yarmouth
NR31 6LA
United Kingdom

Trial participating centre

Kings College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Princess Royal University Hospital
Farnborough Common
Orpington
BR6 8ND
United Kingdom

Trial participating centre

Kings Mill Hospital
Mansfield Road Nottinghamshire
Sutton-In-Ashfield
NG17 4JL
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester General Infirmary Gwendolen Road Leicester LE5 4PW
Leicester
LE5 4PW
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Milton Keynes General Hospital
Standing Way Eaglestone
Milton Keynes
MK6 5LD
United Kingdom

Trial participating centre

Monklands Hospital
Monkscourt Avenue
Airdrie
ML6 0JS
United Kingdom

Trial participating centre

Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Nevill Hall Hospital
Brecon Road
Abergavenny
NP7 7EG
United Kingdom

Trial participating centre

Northampton General Hospital

Northampton
NN1 5BD
United Kingdom

Trial participating centre

Nottingham University Hospitals
City Hospital Campus Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Peterborough City Hospital
Peterborough & Stamford NHS FT Bretton Gate
Peterborough
PE3 9GZ
United Kingdom

Trial participating centre

Poole Hospital
Poole Hospital NHS Foundation Trust Longfleet Road Dorset
Poole
BH15 2JB
United Kingdom

Trial participating centre

Royal Bournemouth Hospital
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham
University Hospital Birmingham NHS Foundation Trust Queen Elizabeth Hospital Queen Elizabeth Medical Centre Edgbaston
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Queen Elizabeth Hospital Gateshead
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom

Trial participating centre

Queen's Hospital Romford
Haematology & Oncology Department Queens Hospital Rom Valley Way Essex
Romford
RM7 0AG
United Kingdom

Trial participating centre

Raigmore Hospital
Department of Haematology Old Perth Road
Inverness
IV2 3UJ
United Kingdom

Trial participating centre

Rotherham District General Hospital
Moorgate Road Oakwood Rotherham S60 2UD
Rotherham
S60 2UD
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Royal Cornwall Hospital

Truro
TR1 3LJ
United Kingdom

Trial participating centre

Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Royal Devon and Exeter Hospital
Barrack Road Devon
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Royal Gwent Hospital
Block 3, Pathology Royal Gwent Hospital Newport Gwent NP20 2UB
Newport
NP20 2UB
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Trial participating centre

Royal Lancaster Infirmary
Ashton Road
Lancaster
LA1 4RP
United Kingdom

Trial participating centre

Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Royal Marsden Hospital
London
London
SW3 6JJ
United Kingdom

Trial participating centre

Royal Oldham Hospital
Central Admin, Pennine Square Rochdale Road
Oldham
OL1 2JH
United Kingdom

Trial participating centre

Royal Stoke University Hospital
Stoke-on-Trent
ST4 6QG
United Kingdom

Trial participating centre

Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom

Trial participating centre

Royal United Hospital
Bath
BA1 3NG
United Kingdom

Trial participating centre

Russells Hall Hospital
Georgina Unit High Street Pensnett
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Salford Royal Hospital
Salford Royal Hospital NHS Foundation Trust Stott Lane Salford Manchester M6 8HD
Salford
M6 8HD
United Kingdom

Trial participating centre

Salisbury District Hospital
Salisbury
SB2 8BJ
United Kingdom

Trial participating centre

Sandwell General Hospital
Lyndon West Midlands
West Bromwich
B71 4HJ
United Kingdom

Trial participating centre

Scunthorpe General Hospital
Cliff Gardens
Scunthorpe
DN15 7BH
United Kingdom

Trial participating centre

Diana, Princess of Wales Hospital
Scartho Road
Grimsby
DN33 2BA
United Kingdom

Trial participating centre

Singleton Hospital
Sketty Lane
Swansea
SA2 8QA
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

St Bartholomew's Hospital
West Smithfield
London
EC1A 7BE
United Kingdom

Trial participating centre

St. James's University Hospital
Department of Haematology, Level 3 Bexley Wing St. James's University Hospital Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

St George's Hospital
London
SW17 0QT
United Kingdom

Trial participating centre

Stoke Mandeville Hospital
CCHU Mandeville Road Buckinghamshire
Aylesbury
HP21 8AL
United Kingdom

Trial participating centre

Torbay District General Hospital
Lawes Bridge South Devon
Torquay
TQ2 7AA
United Kingdom

Trial participating centre

University College London Hospital
235 Euston Road
London
NW1 2BU
United Kingdom

Trial participating centre

University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom

Trial participating centre

University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

University Hospital Coventry
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Victoria Hospital Kirkcaldy
Fife Area Labs Victoria Hospital (Kirkcaldy) Hayfield Road Kirkcaldy Fife KY2 5AH
Kirkcaldy
KY2 5AH
United Kingdom

Trial participating centre

Queen Margaret Hospital
Whitefield Road
Dunfermline
KY12 0SU
United Kingdom

Trial participating centre

Watford General Hospital
Watford
WD18 0HB
United Kingdom

Trial participating centre

West Middlesex University Hospital
Isleworth
TW7 6AF
United Kingdom

Trial participating centre

West Wales General Hospital
Glangwili General Hospital, Chemotherapy Day Unit, Dolgwili Road, Carmarthen, SA31 2AF Glangwili General Hospital Dolgwilli Road Carmarthen Carmarthenshire SA31 2AF
Carmarthen
SA31 2AF
United Kingdom

Trial participating centre

Western General Hospital
Crewe Road
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Worcestershire Royal Hospital
Charles Hastings Way
Worcester
WR5 1DD
United Kingdom

Trial participating centre

Worthing Hospital
Lyndhurst Road
Worthing
BN11 2DH
United Kingdom

Trial participating centre

St Richards Hospital
Spitalfield Lane
Chichester
PO19 6SE
United Kingdom

Trial participating centre

Wythenshawe Hospital
Department of Haematology University Hospital of South Manchester NHS Foundation Trust Southmoor Road Wythenshawe
Manchester
M23 9LT
United Kingdom

Trial participating centre

York Hospital
Wiggington Road
York
YO31 8HE
United Kingdom

Trial participating centre

Ysbyty Gwynedd
Penrhosgarnedd
Bangor
LL57 1PW
United Kingdom

Trial participating centre

Ysbyty Maelor
Wrexham Maelor Hospital Croesnewydd Road
Wrexham
LL13 7TD
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

Clinical Trials Research Unit
Leeds Institute of Clinical Trials Research
Leeds
LS2 9JT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK; Grant Codes: C18027/A15790

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Janssen Pharmaceuticals

Alternative name(s)

Janssen Pharmaceuticals, Inc.

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

AbbVie Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal in 2024.

IPD sharing statement
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28830517

Publication citations

Additional files

Editorial Notes

10/09/2018: The secondary outcome measures have been changed. 07/09/2018: The following changes have been made: 1. The study hypothesis has been changed. 2. The interventions have been changed. 3. The primary outcome measures have been changed. 4. The secondary outcome measures have been changed. 5. The participant exclusion criteria have been changed. 6. 103 UK trial centres have been added. 19/10/2017: Publication reference added. 24/07/2017: Publication and dissemination plan added. 29/06/2017: The following changes were made to the trial record: 1. The title was changed from 'Front-Line therapy in CLL: Assessment of Ibrutinib + Rituximab' to 'Front-Line therapy in CLL: Assessment of Ibrutinib-containing Regimes'. 2. The overall trial end date was changed from 01/08/2018 to 01/01/2030. 3. The target number of participants was changed from 754 to 1576. 4. The recruitment end date was changed from 01/08/2018 to 01/01/2020. 5. AbbVie Ltd was added as a funder. 18/10/2016: The recruitment start date was changed from 01/08/2014 to 01/09/2014.