CLL4 Trial

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CLL4 Trial

LRF CLL4 Trial

Chronic Lymphocytic Leukaemia Trial 4 (CLL4) is an LRF-funded trial from the NCRI Haematological Oncology Clinical Studies Group. MREC (1) 98/101 A RANDOMISED COMPARISON OF CHLORAMBUCIL, FLUDARABINE AND FLUDARABINE PLUS CYCLOPHOSPHAMIDE. ISRCTN number: 58585610. EUDRACT Number: 2004.000105-21.

LRF CLL4 is now closed for both first and second randomisations. However, follow-up continues for patients already recruited into this trial. Investigators are requested to continue to return follow-up form C to the CTSU on an annual basis and to notify the CTSU on 2nd line treatment form (D) about all treatments given to LRF CLL4 participants after relapse.

The quality of life questionnaire and quality of life investigator form should be returned annually up to and including the end of year 5.

Annually in October the CTSU sends a short follow-up form with one line per patient to each investigator. Please return this form promptly each year, even if a form C or form D has recently been completed. This follow-up form allows statistically reliable use of each additional year of follow-up in presentations and publications from the trial.

The CTSU address is as follows:
CTSU
Richard Doll Building
Old Road Campus
Roosevelt Drive
OXFORD
OX3 7LF

Freepost address (for leukaemia trial forms):
Freepost RLUJ-UUUU-UUAC
CTSU
Richard Doll Building
Old Road
Headington
OXFORD
OX3 7LF

Telephone: 01865- 765615
Fax forms to: 01865-743986

For general enquiries contact:

randomisation@ctsu.ox.ac.uk

CTSU website address: www.ctsu.ox.ac.uk

The LRF CLL4 Trial

This study compared conventional therapy with chlorambucil versus the newer agent fludarabine, used alone or in combination with cyclophosphamide. End points of the trial were: survival, response to therapy, duration of response, toxicity and quality of life. For patients who required further treatment after relapse or second line therapy for non-responders, a second randomisation compared treatment guided by the protocol versus guided by the in-vitro drug sensitivity DiSC assay. CLL4 will also provide an opportunity to investigate the prognostic value of four genetic markers by FISH analysis and other factors such as IgVH mutational status, beta2 microglobulin and CD38 and ZAP-70 expression. Between 1999-2004 a total of 777 patients were enrolled in the study.

Publications Reporting the Trial Results

1. 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; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet 370:230-9; 2007.

2. 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 111(4):1820-6; 2008.

3. 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 111(3):1625-33; 2008.

4. Else M, Smith AG, Cocks K, Richards SM, Crofts S, Wade R, Catovsky D, on behalf of the UK NCRI CLL Trials Group. Patients’ experience of chronic lymphocytic leukaemia: baseline health-related quality of life results from the LRF CLL4 trial. British Journal of Haematology 2008 (in press).

Further LRF CLL4 papers in preparation

1. Prognostic factors in the LRF CLL4 trial

2. A comparison of intravenous and oral fludarabine

3. Mutations of the TP53 gene

4. Quality of life: baseline to 5 years

Other papers planned include a report of the second randomisation and a comparison of outcomes by gender.

Trial Forms Still Currently in Use

Follow up form (C) (16 KB)

2nd line treatment form (D) (12 KB)

Quality of life questionnaire (12 KB)

Quality of life investigator form (11 KB)

Trial Closure Documentation