Condition category
Cancer
Date applied
01/07/2001
Date assigned
01/07/2001
Last edited
02/03/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.icr.ac.uk/research/research_sections/haemato_oncology/4448.shtml

Contact information

Type

Scientific

Primary contact

Prof D Catovsky

ORCID ID

Contact details

Section of Haemato-Oncology
Institute of Cancer Research
Brookes Lawley Building
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
+44 (0)20 8722 4114
daniel.catovsky@icr.ac.uk

Additional identifiers

EudraCT number

2004-000105-21

ClinicalTrials.gov number

NCT00004218

Protocol/serial number

LRF CLL4

Study information

Scientific title

Conventional therapy with chlorambucil versus fludarabine, used alone or in a novel combination with cyclophosphamide: a randomised controlled trial

Acronym

CLL 4

Study hypothesis

This study will compare conventional therapy with chlorambucil versus the new agent fludarabine, used alone or in a novel combination with cyclophosphamide. End points of the trial will be:
1. Survival
2. Response to therapy
3. Duration of response
4. Toxicity
5. Quality of life

Ethics approval

South Thames MREC initially approved of this trial in 1998 (ref. no: MREC 98/1/101). An amendment to the protocol was accepted on 27th February 2001.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Chronic lymphocytic leukaemia (CLL)

Intervention

Patients will be randomised between chlorambucil versus fludarabine based treatment. Half of the patients randomised to fludarabine will be randomised between fludarabine plus cyclophosphamide and fludarabine alone.

Intervention type

Drug

Phase

Not Specified

Drug names

Chlorambucil, fludarabine, fludarabine, cyclophosphamide

Primary outcome measures

Survival

Secondary outcome measures

1. Response to therapy
2. Duration of response
3. Toxicity
4. Quality of life

Overall trial start date

01/02/1999

Overall trial end date

30/10/2004

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients are diagnosed with B-cell chronic lymphocytic leukaemia
2. They have not previously been treated
3. They have been diagnosed by a persistent lymphocytosis and bone marrow infiltration of at least 40% and require treatment
4. They are classified as having stage A progressive, stage B or stage C disease using the International Binet Staging System
5. They have given informed consent

Participant type

Patient

Age group

Not Specified

Gender

Both

Target number of participants

750 (initially 500)

Participant exclusion criteria

1. Patients with other life-threatening diseases
2. Patients unable or unwilling to give informed consent
3. Renal failure (creatinine clearance less than 30 ml/min)
4. Hepatic enzymes and bilirubin greater than twice the upper limit of normal, unless due to CLL
5. Pregnant women or women at risk of pregnancy
6. Patients who for other reasons are not expected to complete the study
7. Patients with a diagnosis other than CLL after central review of markers and morphology

Recruitment start date

01/02/1999

Recruitment end date

30/10/2004

Locations

Countries of recruitment

Argentina, Croatia, Greece, Ireland, Italy, New Zealand, Russian Federation, United Kingdom

Trial participating centre

Section of Haemato-Oncology
Sutton
SM2 5NG
United Kingdom

Sponsor information

Organisation

Institute of Cancer Research (UK)

Sponsor details

c/o Professor D Catovsky
Section of Haemato-Oncology
Brookes Lawley Building
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
+44 (0)20 8722 4114
daniel.catovsky@icr.ac.uk

Sponsor type

Research organisation

Website

http://www.icr.ac.uk/

Funders

Funder type

Charity

Funder name

Leukaemia Research Fund (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

1. 2007 results of assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia in http://www.ncbi.nlm.nih.gov/pubmed/17658394
2. 2008 results on the prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia in http://www.ncbi.nlm.nih.gov/pubmed/18055869
3. 2008 results on the scan of nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis in http://www.ncbi.nlm.nih.gov/pubmed/18006695
4. 2008 results on baseline health-related quality of life in http://www.ncbi.nlm.nih.gov/pubmed/19016733
5. 2010 results of identification of prognostic makers in http://www.ncbi.nlm.nih.gov/pubmed/20511662
6. 2010 results of relative importance of prognostic makers in http://www.ncbi.nlm.nih.gov/pubmed/20511662

Publication citations

  1. Results of relative importance of prognostic makers

    Oscier D, Wade R, Davis Z, Morilla A, Best G, Richards S, Else M, Matutes E, Catovsky D, , Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation., Haematologica, 2010, 95, 10, 1705-1712, doi: 10.3324/haematol.2010.025338.

  2. Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P, , , Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial., Lancet, 2007, 370, 9583, 230-239, doi: 10.1016/S0140-6736(07)61125-8.

  3. Dearden C, Wade R, Else M, Richards S, Milligan D, Hamblin T, Catovsky D, , , , The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia., Blood, 2008, 111, 4, 1820-1826, doi: 10.1182/blood-2007-07-101303.

  4. Sellick GS, Wade R, Richards S, Oscier DG, Catovsky D, Houlston RS, Scan of 977 nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis., Blood, 2008, 111, 3, 1625-1633, doi: 10.1182/blood-2007-08-110130.

  5. Else M, Smith AG, Cocks K, Richards SM, Crofts S, Wade R, Catovsky D, Patients' experience of chronic lymphocytic leukaemia: baseline health-related quality of life results from the LRF CLL4 trial., Br. J. Haematol., 2008, 143, 5, 690-697, doi: 10.1111/j.1365-2141.2008.07407.x.

Additional files

Editorial Notes