Alternative Ofatumumab containing regimens in less fit patients with chronic lymphoid leukemia (CLL)

ISRCTN	ISRCTN09988575
DOI	https://doi.org/10.1186/ISRCTN09988575
EudraCT/CTIS number	2011-000919-22
ClinicalTrials.gov number	NCT01678430
Secondary identifying numbers	11159

Submission date: 28/10/2011
Registration date: 28/10/2011
Last edited: 02/05/2025

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://cancerhelp.cancerresearchuk.org/trials/trials-search/a-trial-looking-ofatumumab-people-chronic-lymphocytic-leukaemia-who-cannot-have-more-intensive-treatment-rialto

Contact information

Miss Kathryn Marley
Scientific

Liverpool CR-UK Centre
University of Liverpool
Block C, Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Email	kathryn.marley@liv.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment
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	A Randomised Investigation of Alternative Ofatumumab containing regimens in less fit patients with chronic lymphoid leukemia (CLL)
Study acronym	RIAltO
Study hypothesis	This is a randomised, controlled, phase III trial comparing ofatumumab and chlorambucil (OChl) with ofatumumab and bendamustine (OB) in patients with chronic lymphocytic leukaemia (CLL) who are considered not fit enough to receive more intensive combination chemotherapy. The primary purpose of the trial is to establish if OB is more effective at prolonging the worsening of the disease than OChl.
Ethics approval(s)	NRES Committee North West - Haydock, First MREC approval date 14/09/2011, ref: 11/NW/0548
Condition	Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)
Intervention	670 patients are to be enrolled in total (335 per treatment arm) from approximately 100 centres throughout the United Kingdom. Patients will receive between 3 12 cycles of treatment depending on which treatment arm they are allocated to and how well they respond to the treatment. The schedule of treatment is as follows: Arm 1: OChl repeated every 28 days for up to 12 cycles depending on clinical response after cycles 3, 6 and 9. Arm 2: OB repeated every 28 days for up to 6 cycles depending on clinical response after cycle 3. All patients will be followed up for a minimum of 2 years from trial entry. All laboratory and physical assessments are routine for CLL but additional scientific tests may be performed when specific consent has been given. Ofatumumab and 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 Cycles to be repeated every 28 days, up to 6 cycles depending on clinical response after cycle 3; Ofatumumab and Chlorambucil, Ofatumumab cycle 1: 300mg IV day, 100mg iv day 8 cycle 2 onwards: 1000mg iv day 1 Chlorambucil: 10mg/m2 po days 1 to 7 Cycles to be repeated every 28 days, up to 12 cycles depending on clinical response after cycles 3, 6 & 9; Follow Up Length: 24 month(s)
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Ofatumumab, chlorambucil, bendamustine
Primary outcome measure	Progression-free survival; Timepoint(s): End of trial
Secondary outcome measures	1. Comorbidity assessment; Timepoint(s): Baseline; cycles 4, 7 & 10; 2 months post treatment 2. Disease progression; Duration of response; Timepoint(s): Cycles 4, 7 & 10; 2 & 6 months post treatment; end of trial 3. Frailty assessment; Timepoint(s): Baseline 4. Health economic analysis; Timepoint(s): Every 3 months until end of trial 5. Overall survival; Timepoint(s): End of trial 6. Predictive value of biomarkers; Timepoint(s): Baseline; months 6, 12, 18, 24, 36, 42 7. Disease progression 8. Quality of life; Timepoint(s): Every 3 months until end of trial 9. Response including Minimum Residual Disease (MRD) negativity; Timepoint(s): Cycles 4, 7 & 10; 2 & 6 months post treatment 10. Time to treatment failure; Timepoint(s): Cycles 4, 7 & 10; 2 & 6 months post treatment; end of trial 11. Toxicity; Timepoint(s): Every visit until 6 months post treatment 12. Treatment dose administered; Timepoint(s): End of treatment
Overall study start date	01/12/2011
Overall study end date	30/04/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	Planned Sample Size: 670; UK Sample Size: 670
Participant inclusion criteria	1. CLL requiring treatment by National Cancer Institute/International Workshop on Chronic Lymphocytic Leukemia (NCI/IWCLL) 2008 criteria. At least one of the following criteria: 1.1. Progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia 1.2. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly 1.3. Massive (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy 1.4. 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 therapy for CLL 3. Full-dose rituximab-fludarabine, cyclophosphamide (R-FC) considered inappropriate for at least one of the following reasons 3.1. Age 75 or greater 3.2. WHO performance status 2 or 3 3.3. Cardiac impairment (New York Heart Association (NYHA) class II) 3.4. Respiratory impairment (bronchiectasis or moderate Chronic obstructive pulmonary disease (COPD)) 3.5. Renal impairment (estimated Glomerular Filtration Rate (eGFR) 10-30 ml/min) 3.6. Any other significant co-morbidity or factor that makes R-FC inappropriate 4. Considered able to tolerate chlorambucil (Chl) at the dose used in the LRF CLL4 trial (10mg/m2 d1-7) 5. Written informed consent ; Lower Age Limit 16 no age limit or unit specified
Participant 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 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 Gilberts 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.
Recruitment start date	01/12/2011
Recruitment end date	30/04/2018

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Liverpool CRUK Centre

Liverpool
L69 3GL
United Kingdom

Sponsor information

Royal Brompton & Harefield NHS Foundation Trust
University/education

Cancer Research UK Liverpool Cancer Trials Unit
University of Liverpool
1st floor Block C
Waterhouse Building 3 Brownlow Street
London
SW3 6NP
England
United Kingdom

Website	http://www.rbht.nhs.uk/
"ROR"	https://ror.org/02218z997

Royal Liverpool and Broadgreen University Hospitals NHS Trust
Hospital/treatment centre

c/o Heather Rogers
Prescot Street
Liverpool
L7 8XP
England
United Kingdom

Funders

Funder type

Industry

GlaxoSmithKline
Government organisation / For-profit companies (industry)

Alternative name(s): GlaxoSmithKline plc., GSK plc., GSK
Location: United Kingdom

Napp Pharmaceuticals (UK)

No information available

Chugai Pharma UK Ltd (UK)

No information available

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?
Results article	results	01/06/2017		Yes	No
HRA research summary			28/06/2023	No	No
Results article		17/04/2025	02/05/2025	Yes	No

Editorial Notes

02/05/2025: Publication reference added.
07/03/2018: Publication reference added.
12/01/2018: The overall trial end date was changed from 01/12/2015 to 30/04/2018.