A Trial Looking at Ofatumumab for People With Chronic Lymphocytic Leukaemia Who Cannot Have More Intensive Treatment
RIAltO
A Randomised Investigation of Alternative Ofatumumab-containing Regimens in Less Fit Patients With CLL
3 other identifiers
interventional
670
1 country
28
Brief Summary
The purpose of this study is to compare ofatumumab \& chlorambucil (O-Chl) versus ofatumumab \& bendamustine (O-B) in patients with Chronic Lymphocytic Leukaemia who are considered not fit enough for rituximab, fludarabine \& cyclophosphamide (R-FC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2011
Longer than P75 for phase_3
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2011
CompletedFirst Submitted
Initial submission to the registry
August 30, 2012
CompletedFirst Posted
Study publicly available on registry
September 5, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2017
CompletedOctober 15, 2012
August 1, 2012
6 years
August 30, 2012
October 12, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival
Calculated from the date of randomisation to the date of progression or death, or the censor date.
There are three pre-planned analyses of the PFS primary endpoint: end recruitment (approx 150 events); 300 events (after a minimum 12 months follow up for all patients), 400 events (after a minimum 24 months follow up for all patients)
Secondary Outcomes (10)
Duration of response
6 years (after 2 years follow up of the last patient recruited)
Overall survival
6 years (after 2 year follow up of the last patient recruited)
Time to treatment failure
6 years (after 2 year follow up of the last patient recruited)
Toxicity
6 years (after 2 years follow up of the last patient recruited)
Treatment dose administered
5 years (assuming last patient in receives 12 cycles of treatment)
- +5 more secondary outcomes
Study Arms (2)
Ofatumumab-Chlorambucil
ACTIVE COMPARATOROfatumumab cycle 1: 300mg iv day 1, 1000mg iv day 8; cycle 2 onwards: 1000mg iv day 1 Chlorambucil: 10mg/m2 po days 1-7
Ofatumumab-Bendamustine
EXPERIMENTALOfatumumab cycle 1: 300mg iv day 1, 1000mg iv day 8; cycle 2 onwards: 1000mg iv day 1 Bendamustine: 70mg/m2 iv days 1 and 2
Interventions
Eligibility Criteria
You may qualify if:
- CLL/SLL requiring treatment by NCI/IWCLL 2008 criteria. At least one of the following criteria:
- Progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.
- Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
- Massive (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
- Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
- No prior cytotoxic or targeted therapy for CLL
- Full-dose R-FC considered inappropriate for at least one of the following reasons
- Age 75 or greater
- WHO performance status 2 or 3
- Cardiac impairment (NYHA class II)
- Respiratory impairment (bronchiectasis or moderate COPD)
- Renal impairment (estimated Glomerular Filtration Rate (eGFR) 10-30 ml/min)
- Any other significant co-morbidity or factor that makes R-FC inappropriate
- Considered able to tolerate Chl at the dose used in the LRF CLL4 trial (10mg/m2 d1-7)
- Written informed consent
You may not qualify if:
- Neutrophil count less than 1.0 x 109/l or platelet count less than 50 x 109/l unless due to CLL
- Uncontrolled auto-immune haemolytic anaemia or thrombocytopenia
- Active infection
- Seropositivity for HIV, HCV or HBV (surface antigen or and core antibody)
- Severe renal impairment (eGFR less than 10ml/min)
- Severe hepatic impairment (serum bilirubin more than twice the upper limit of normal) unless due to CLL or Gilbert's syndrome.
- Concurrent treatment with glucocorticoids equivalent to more than prednisolone 20mg od
- Prior treatment with monoclonal antibody therapy within the last 3 months.
- Yellow fever vaccination within 4 weeks prior to treatment start
- Known hypersensitivity to ofatumumab, bendamustine or chlorambucil or any of their excipients
- CNS involvement with CLL
- History of Richter transformation
- Concomitant malignancies within the last 3 years except successfully treated non-melanoma skin cancer or carcinoma in situ.
- Major surgery within 28 days prior to randomisation
- WHO performance status 4
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Liverpoollead
- GlaxoSmithKlinecollaborator
- Napp Pharmaceuticals Limitedcollaborator
- Chugai Pharma USAcollaborator
Study Sites (28)
Countess of Chester Hospital
Chester, Cheshire, United Kingdom
Derriford Hospital
Plymouth, Devon, United Kingdom
Torbay Hospital
Torquay, Devon, United Kingdom
Royal Bournemouth Hospital
Bournemouth, Dorset, United Kingdom
Dorset County Hospital
Dorchester, Dorset, United Kingdom
Colchester General Hospital
Colchester, Essex, United Kingdom
Basingstoke and North Hampshire Hospital
Basingstoke, Hampshire, United Kingdom
Southampton General Hospital
Southampton, Hampshire, United Kingdom
Barnet and Chase Farm Hospitals
Enfield, Hertfordshire, United Kingdom
Kent and Canterbury Hospital
Canterbury, Kent, United Kingdom
Maidstone Hospital
Maidstone, Kent, United Kingdom
Princess Royal Hospital
Orpington, Kent, United Kingdom
Queen Elizabeth Hospital
Woolwich, London, United Kingdom
West Middlesex University Hospital
Isleworth, Middlesex, United Kingdom
Ealing Hospital
Southall, Middlesex, United Kingdom
Hillingdon Hospital
Uxbridge, Middlesex, United Kingdom
Belfast City Hospital
Belfast, Northern Ireland, United Kingdom
Royal United Hospital
Bath, Somerset, United Kingdom
Weston General Hospital
Weston-super-Mare, Somerset, United Kingdom
Queens Hospital
Burton-on-Trent, Staffordshire, United Kingdom
Queen Elizabeth Hospital
Gateshead, Tyne and Wear, United Kingdom
Queen Elizabeth Hospital
Birmingham, West Midlands, United Kingdom
Bradford Royal Infirmary
Bradford, West Yorkshire, United Kingdom
Airdale General Hospital
Keighley, West Yorkshire, United Kingdom
St James University Hospital
Leeds, West Yorkshire, United Kingdom
Salisbury District Hospital
Salisbury, Wiltshire, United Kingdom
Arrowe Park Hospital
Upton, Wirral, United Kingdom
Royal Liverpool Hospital
Liverpool, United Kingdom
Related Publications (1)
Lim YJ, Duckworth AD, Clarke K, Kennedy P, Karpha I, Oates M, Gornall M, Kalakonda N, Slupsky JR, Pettitt AR. Influence of polyfunctional Tbet+ T cells on specific clinical events in chronic lymphocytic leukaemia. Front Immunol. 2025 Apr 17;16:1528405. doi: 10.3389/fimmu.2025.1528405. eCollection 2025.
PMID: 40313965DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
August 30, 2012
First Posted
September 5, 2012
Study Start
December 1, 2011
Primary Completion
December 1, 2017
Study Completion
December 1, 2017
Last Updated
October 15, 2012
Record last verified: 2012-08