Condition category
Cancer
Date applied
28/10/2011
Date assigned
28/10/2011
Last edited
02/05/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Miss Kathryn Marley

ORCID ID

Contact details

Liverpool CR-UK Centre
University of Liverpool
Block C
Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
kathryn.marley@liv.ac.uk

Additional identifiers

EudraCT number

2011-000919-22

ClinicalTrials.gov number

Protocol/serial number

11159

Study information

Scientific title

A Randomised Investigation of Alternative Ofatumumab containing regimens in less fit patients with chronic lymphoid leukemia (CLL)

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

NRES Committee North West - Haydock, First MREC approval date 14/09/2011, ref: 11/NW/0548

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 below to request a patient information sheet

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)

Details of Co-Sponsor:
Royal Liverpool and Broadgreen University Hospitals NHS Trust
c/o Heather Rogers
Prescot Street
Liverpool
L7 8XP
United Kingdom

Intervention type

Drug

Phase

Phase III

Drug names

Ofatumumab, chlorambucil, bendamustine

Primary outcome measures

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 trial start date

01/12/2011

Overall trial end date

01/12/2015

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 670; UK Sample Size: 670

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 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.

Recruitment start date

01/12/2011

Recruitment end date

01/12/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Liverpool CR-UK Centre
Liverpool
L69 3GL
United Kingdom

Sponsor information

Organisation

University of Liverpool (UK)

Sponsor details

Cancer Research UK Liverpool Cancer Trials Unit
University of Liverpool
1st floor Block C
Waterhouse Building 3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Glaxo-SmithKline (GSK) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Napp Pharmaceuticals (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Chugai Pharma UK Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes