A Trial Looking at Ofatumumab for People With Chronic Lymphocytic Leukaemia Who Cannot Have More Intensive Treatment

NCT ID: NCT01678430

Last Updated: 2012-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

670 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2017-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Chlorambucil (Chl) has been the mainstay of CLL treatment for half a century. However, frontline treatment has improved considerably over the last decade, first by the advent of fludarabine plus cyclophosphamide (FC), and more recently by the addition of the anti-CD20 antibody, rituximab, to FC. Although FC-based regimens are considerably more effective than Chl, they are also associated with greater toxicity which makes them inappropriate for less fit patients. This is an important consideration, given that CLL predominantly affects older people who tend to have more co-morbidity. Although a single-arm phase II study (Roche MO20927; NCRI CLL208) has shown that R-Chl is safe and effective, there are no phase III data proving the benefit of adding an anti-CD20 antibody to Chl. This question is currently being addressed by a phase III RCT of Chl with or without ofatumumab (GSK OMB110911 / COMPLEMENT-1 / NCRI CLL7). Ofatumumab is a fully human anti-CD20 antibody that binds to an epitope distinct from that of rituximab and produces more complement-dependent cytotoxicity. The RIAltO trial is a direct follow-on to the NCRI CLL7 phase III RCT trial in less fit patients and therefore the Ofatumumab dose has been selected to mirror the regimen used in that trial.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Lymphocytic Leukaemia

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Chronic Lymphocytic Leukaemia Less fit CD20 antibody Ofatumumab Chlorambucil Bendamustine

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ofatumumab-Chlorambucil

Ofatumumab cycle 1: 300mg iv day 1, 1000mg iv day 8; cycle 2 onwards: 1000mg iv day 1 Chlorambucil: 10mg/m2 po days 1-7

Group Type ACTIVE_COMPARATOR

Ofatumumab

Intervention Type DRUG

Chlorambucil

Intervention Type DRUG

Ofatumumab-Bendamustine

Ofatumumab 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

Group Type EXPERIMENTAL

Ofatumumab

Intervention Type DRUG

Bendamustine

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ofatumumab

Intervention Type DRUG

Chlorambucil

Intervention Type DRUG

Bendamustine

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Arzerra Leukeran Levact

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. CLL/SLL requiring treatment by NCI/IWCLL 2008 criteria. At least one of the following criteria:

1. Progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.
2. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
3. Massive (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
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.
2. No prior cytotoxic or targeted therapy for CLL
3. Full-dose R-FC considered inappropriate for at least one of the following reasons

1. Age 75 or greater
2. WHO performance status 2 or 3
3. Cardiac impairment (NYHA class II)
4. Respiratory impairment (bronchiectasis or moderate COPD)
5. Renal impairment (estimated Glomerular Filtration Rate (eGFR) 10-30 ml/min)
6. Any other significant co-morbidity or factor that makes R-FC inappropriate
4. Considered able to tolerate Chl at the dose used in the LRF CLL4 trial (10mg/m2 d1-7)
5. Written informed consent

Exclusion Criteria

1. Neutrophil count less than 1.0 x 109/l or platelet count less than 50 x 109/l unless due to CLL
2. Uncontrolled auto-immune haemolytic anaemia or thrombocytopenia
3. Active infection
4. Seropositivity for HIV, HCV or HBV (surface antigen or and core antibody)
5. Severe renal impairment (eGFR less than 10ml/min)
6. Severe hepatic impairment (serum bilirubin more than twice the upper limit of normal) unless due to CLL or Gilbert's syndrome.
7. Concurrent treatment with glucocorticoids equivalent to more than prednisolone 20mg od
8. Prior treatment with monoclonal antibody therapy within the last 3 months.
9. Yellow fever vaccination within 4 weeks prior to treatment start
10. Known hypersensitivity to ofatumumab, bendamustine or chlorambucil or any of their excipients
11. CNS involvement with CLL
12. History of Richter transformation
13. Concomitant malignancies within the last 3 years except successfully treated non-melanoma skin cancer or carcinoma in situ.
14. Major surgery within 28 days prior to randomisation
15. WHO performance status 4
16. Severe cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia (excluding extra systoles or minor conduction abnormalities) unless controlled by therapy.
17. Any serious underlying medical or psychological conditions, which could impair the ability of the patient to participate in the trial or compromise ability to give informed consent
18. Treatment within a clinical trial within 30 days prior to trial entry.
19. Adult patient under tutelage (not competent to sign informed consent).
20. Pregnant or lactating women.
21. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
22. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Napp Pharmaceuticals Limited

INDUSTRY

Sponsor Role collaborator

Chugai Pharma USA

INDUSTRY

Sponsor Role collaborator

University of Liverpool

OTHER

Sponsor Role lead

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Countess of Chester Hospital

Chester, Cheshire, United Kingdom

Site Status RECRUITING

Derriford Hospital

Plymouth, Devon, United Kingdom

Site Status RECRUITING

Torbay Hospital

Torquay, Devon, United Kingdom

Site Status RECRUITING

Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom

Site Status RECRUITING

Dorset County Hospital

Dorchester, Dorset, United Kingdom

Site Status RECRUITING

Colchester General Hospital

Colchester, Essex, United Kingdom

Site Status RECRUITING

Basingstoke and North Hampshire Hospital

Basingstoke, Hampshire, United Kingdom

Site Status RECRUITING

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Site Status RECRUITING

Barnet and Chase Farm Hospitals

Enfield, Hertfordshire, United Kingdom

Site Status RECRUITING

Kent and Canterbury Hospital

Canterbury, Kent, United Kingdom

Site Status RECRUITING

Maidstone Hospital

Maidstone, Kent, United Kingdom

Site Status RECRUITING

Princess Royal Hospital

Orpington, Kent, United Kingdom

Site Status RECRUITING

Queen Elizabeth Hospital

Woolwich, London, United Kingdom

Site Status RECRUITING

West Middlesex University Hospital

Isleworth, Middlesex, United Kingdom

Site Status RECRUITING

Ealing Hospital

Southall, Middlesex, United Kingdom

Site Status RECRUITING

Hillingdon Hospital

Uxbridge, Middlesex, United Kingdom

Site Status RECRUITING

Belfast City Hospital

Belfast, Northern Ireland, United Kingdom

Site Status RECRUITING

Royal United Hospital

Bath, Somerset, United Kingdom

Site Status RECRUITING

Weston General Hospital

Weston-super-Mare, Somerset, United Kingdom

Site Status RECRUITING

Queens Hospital

Burton-on-Trent, Staffordshire, United Kingdom

Site Status RECRUITING

Queen Elizabeth Hospital

Gateshead, Tyne and Wear, United Kingdom

Site Status RECRUITING

Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

Site Status RECRUITING

Bradford Royal Infirmary

Bradford, West Yorkshire, United Kingdom

Site Status RECRUITING

Airdale General Hospital

Keighley, West Yorkshire, United Kingdom

Site Status RECRUITING

St James University Hospital

Leeds, West Yorkshire, United Kingdom

Site Status RECRUITING

Salisbury District Hospital

Salisbury, Wiltshire, United Kingdom

Site Status RECRUITING

Arrowe Park Hospital

Upton, Wirral, United Kingdom

Site Status RECRUITING

Royal Liverpool Hospital

Liverpool, , United Kingdom

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Kathryn Marley

Role: CONTACT

Phone: +44 151 895 5287

Email: [email protected]

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40313965 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2011-000919-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

009988575

Identifier Type: REGISTRY

Identifier Source: secondary_id

OMB114578

Identifier Type: -

Identifier Source: org_study_id