Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

NCT00004218 | Completed Phase 3

• 7 other identifiers: CDR0000067454LRF-CLL4LRG-MRC-LEUK-CLL4EU-99030MRC-LEUK-CLL4EUDRACT-58585610ISRCTN58585610
• Study Type: interventional
• Target: N/A
• Locations: 8 countries
• Sites: 86

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for chronic lymphocytic leukemia. PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared to fludarabine and cyclophosphamide or fludarabine alone in treating patients with newly diagnosed chronic lymphocytic leukemia.

Conditions

Leukemia

Keywords

stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia; stage 0 chronic lymphocytic leukemia

Interventions

chlorambucil DRUG

cyclophosphamide DRUG

doxorubicin hydrochloride DRUG

fludarabine phosphate DRUG

prednisolone DRUG

vincristine sulfate DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of B-cell chronic lymphocytic leukemia (CLL) requiring therapy and meeting the following criteria: * Previously untreated disease * Peripheral blood morphology, excluding other leukemia and low-grade lymphoma in leukemic phase * Cell markers: CD5+, CD23+, SmIg (weak), CD79b-, FMC7- * Persistent lymphocytosis (greater than 10,000/mm\^3) * At least 40% bone marrow infiltration * Stage 0 or I progressive disease indicated by at least one of the following: * Persistent rise in lymphocyte count with doubling time less than 12 months * Downward trend in hemoglobin and/or platelet count * At least 50% increase in size of liver and/or spleen and/or lymph nodes * Appearance of lymphadenopathy, hepatomegaly, or splenomegaly * Constitutional symptoms caused by disease * Pyrexia * Night sweats * Weight loss OR * Stage II or III PATIENT CHARACTERISTICS: Age: * Not specified Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * Bilirubin no greater than 2 times upper limit of normal (ULN)\* * SGOT/SGPT no greater than 2 times ULN\* NOTE: \* Unless due to CLL Renal: * Creatinine clearance at least 30 mL/min Other: * No other cancer or life-threatening disease * Not pregnant * Fertile patients must use effective contraception during and for 6 months after study therapy PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * No concurrent corticosteroids (e.g., dexamethasone) as antiemetics Radiotherapy * Not specified Surgery * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Leukemia Research Fund: lead
• Medical Research Council: collaborator

Study Sites (86)

Hospital Italiano de Buenos Aires

Buenos Aires, CP1181ACH, Argentina

Location

Hospital Alvarez

Buenos Aires, Argentina

Location

University Hospital Rebro

Zagreb, 10000, Croatia

Location

University of Ioannina

Ioannina, GR-45110, Greece

Location

University of Patras Medical School

Rio Patras, GR-26500, Greece

Location

St. James' Hospital

Dublin, 8, Ireland

Location

Galway University Hospital

Galway, Ireland

Location

Ospedali Riuniti di Bergamo

Bergamo, 24100, Italy

Location

Canterbury Health Laboratories

Christchurch, New Zealand

Location

Russian Academy of Medical Sciences Cancer Research Center

Moscow, 115478, Russia

Location

Stoke Mandeville Hospital

Aylesbury-Buckinghamshire, England, HP21 8AL, United Kingdom

Location

Horton Hospital

Banbury, England, OX16 9A, United Kingdom

Location

North Hampshire Hospital

Basingstoke, England, RG24 9NA, United Kingdom

Location

Selly Oak Hospital at University Hospital NHS Trust

Birmingham, England, B29 6JD, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, England, FY3 8NR, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, England, BH7 7DW, United Kingdom

Location

Bradford Hospitals NHS Trust

Bradford, England, BD9 6RJ, United Kingdom

Location

Royal Sussex County Hospital

Brighton, England, BN2 5BE, United Kingdom

Location

Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

St Helier Hospital

Carshalton, England, SM5 1AA, United Kingdom

Location

Countess of Chester Hospital

Chester, England, CH2 1UL, United Kingdom

Location

Chesterfield Royal Hospital

Chesterfield, England, S44 5BL, United Kingdom

Location

Saint Richards Hospital

Chichester, England, P019 4SE, United Kingdom

Location

Darlington Memorial

Darlington, England, DL3 6HX, United Kingdom

Location

Dartford & Gravesham NHS Trust, Joyce Green Hospital

Dartford Kent, England, DA1 5PL, United Kingdom

Location

Doncaster Royal Infirmary

Doncaster, England, DN2 5LT, United Kingdom

Location

Russells Hall Hospital

Dudley, England, DY1 2HQ, United Kingdom

Location

Bishop Auckland Hospital

Durham, England, United Kingdom

Location

Epsom General Hospital

Epsom Surrey, England, KT18 7E9, United Kingdom

Location

Queen Elizabeth Hospital

Gateshead, England, NE9 6SX, United Kingdom

Location

Queen Elizabeth Hospital

Gateshead-Tyne and Wear, England, NE9 6SX, United Kingdom

Location

Gloucester Royal NHS Trust - Glouchester Royal Hospital

Gloucester, England, GL1 3NN, United Kingdom

Location

St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford, England, GU2 5XX, United Kingdom

Location

Harrogate District Hospital

Harrogate, England, HG2 7SX, United Kingdom

Location

Hemel Hempstead General

Hemel Hempstead, England, United Kingdom

Location

Institute of Oncology and Radiology of Serbia

High Wycombe, England, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, HD3 3EA, United Kingdom

Location

Hull Royal Infirmary

Hull, England, HU3 2KZ, United Kingdom

Location

Clinical Trials and Research Unit of the University of Leeds

Leeds, England, LS2 9N9, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Royal Liverpool and Broadgreen Hospitals

Liverpool, England, L7 8XP, United Kingdom

Location

Walton General Hospital

Liverpool, England, L9 1AE, United Kingdom

Location

Aintree University Hospital

Liverpool, England, L9 7AL, United Kingdom

Location

Whipps Cross Hospital

London, England, E11 1NR, United Kingdom

Location

Royal Free and University College Medical School

London, England, NW1 2QG, United Kingdom

Location

Guy's and St. Thomas' Hospitals NHS Foundation Trust

London, England, SE1 9RT, United Kingdom

Location

St. George's Hospital

London, England, SW17 0QT, United Kingdom

Location

Royal Marsden NHS Foundation Trust - London

London, England, SW3 6JJ, United Kingdom

Location

West Middlesex Hospital

Middlesex, England, N18 1QZ, United Kingdom

Location

Northern Cancer Network

Newcastle upon Tyne, England, NE27 OQJ, United Kingdom

Location

Northampton General Hospital NHS Trust

Northampton, England, NN1 5BD, United Kingdom

Location

Nottingham City Hospital NHS Trust

Nottingham, England, NG5 1PB, United Kingdom

Location

Bassetlaw Hospital & Community Services NHS Trust

Nottinghamshire, England, S81 3SA, United Kingdom

Location

Farnborough Hospital

Orpington Kent, England, BR6 8ND, United Kingdom

Location

Wharfdale General Hospital

Otley, England, LS21 7AA, United Kingdom

Location

Pontefract General Infirmary

Pontefract West Yorkshire, England, WF8 1PL, United Kingdom

Location

Berkshire Cancer Centre at Royal Berkshire Hospital

Reading, England, RG1 5AN, United Kingdom

Location

Oldchurch Hospital

Romford, England, RM7 OBE, United Kingdom

Location

Rotherham District General Hospital - NHS Trust

Rotherham, England, S60 2UD, United Kingdom

Location

Conquest Hospital

Saint Leonards-on-Sea, England, TN37 7RD, United Kingdom

Location

Scunthorpe General Hospital

Scunthorpe, England, DN15 7BH, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Staffordshire General Hospital

Stafford, England, ST16 3SA, United Kingdom

Location

North Staffs Royal Infirmary

Stoke-on-Trent, England, ST4 7LN, United Kingdom

Location

St. Peter's Hospital NHS Trust

Surrey, England, KT 16 OPZ, United Kingdom

Location

Torbay Hospital

Torquay Devon, England, TQ2 7AA, United Kingdom

Location

City Hospital - Birmingham

West Bromwich, England, B71 4HJ, United Kingdom

Location

Good Hope Hospital Trust

West Midlands, England, B75 7RR, United Kingdom

Location

Worthing Hospital

Worthing, England, BN11 2DH, United Kingdom

Location

Cancer Care Centre at York Hospital

York, England, Y031 8HE, United Kingdom

Location

Belfast City Hospital Trust

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Ulster Hospital

Dundonald, Northern Ireland, BT16, United Kingdom

Location

Craigavon Area Hospital

Portadown, Craigavon, Northern Ireland, BT63 5QQ, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Monklands General Hospital

Airdrie, Scotland, ML6 0JF, United Kingdom

Location

Dumfries Royal Infirmary

Dumfries, Scotland, DG1 4AP, United Kingdom

Location

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Southern General Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Raigmore Hospital

Inverness, Scotland, 1V2 3UJ, United Kingdom

Location

Victoria Hospital

Kirkcaldy, Scotland, KY2 5AH, United Kingdom

Location

Royal Alexandra Hospital

Paisley, Scotland, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

Nevill Hall Hospital

Gwent, Wales, United Kingdom

Location

Singleton Hospital

Swansea, Wales, SA 2 8QA, United Kingdom

Location

Related Publications (8)

• Else M, Cocks K, Crofts S, Wade R, Richards SM, Catovsky D, Smith AG; UK National Cancer Research Institute (NCRI) Chronic Lymphocytic Leukaemia Trials Group. Quality of life in chronic lymphocytic leukemia: 5-year results from the multicenter randomized LRF CLL4 trial. Leuk Lymphoma. 2012 Jul;53(7):1289-98. doi: 10.3109/10428194.2011.649479. Epub 2012 Mar 1.

  PMID: 22168274 RESULT

• Gonzalez D, Martinez P, Wade R, Hockley S, Oscier D, Matutes E, Dearden CE, Richards SM, Catovsky D, Morgan GJ. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. J Clin Oncol. 2011 Jun 1;29(16):2223-9. doi: 10.1200/JCO.2010.32.0838. Epub 2011 Apr 11.

  PMID: 21483000 RESULT

• Wade R, Di Bernardo MC, Richards S, Rossi D, Crowther-Swanepoel D, Gaidano G, Oscier DG, Catovsky D, Houlston RS. Association between single nucleotide polymorphism-genotype and outcome of patients with chronic lymphocytic leukemia in a randomized chemotherapy trial. Haematologica. 2011 Oct;96(10):1496-503. doi: 10.3324/haematol.2011.043471. Epub 2011 Jun 9.

  PMID: 21659360 RESULT

• Oscier D, Wade R, Davis Z, Morilla A, Best G, Richards S, Else M, Matutes E, Catovsky D; Chronic Lymphocytic Leukaemia Working Group, UK National Cancer Research Institute. Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation. Haematologica. 2010 Oct;95(10):1705-12. doi: 10.3324/haematol.2010.025338. Epub 2010 May 29.

  PMID: 20511662 RESULT

• 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 Dec;143(5):690-7. doi: 10.1111/j.1365-2141.2008.07407.x. Epub 2008 Oct 18.

  PMID: 19016733 RESULT

• Catovsky D, Richards S, Matutes E, Oscier D, Dyer M, 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. 2007 Jul 21;370(9583):230-239. doi: 10.1016/S0140-6736(07)61125-8.

  PMID: 17658394 RESULT

• Dearden CE, Wade RL, Else M, et al.: The combination of fludarabine and cyclophosphamide has a beneficial effect on the incidence of hemolytic anemia in chronic lymphocytic leukemia: results from the UK LRF CLL4 trial. [Abstract] Blood 110 (11): A-2044, 2007.

  RESULT

• Skowronska A, Parker A, Ahmed G, Oldreive C, Davis Z, Richards S, Dyer M, Matutes E, Gonzalez D, Taylor AM, Moss P, Thomas P, Oscier D, Stankovic T. Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial. J Clin Oncol. 2012 Dec 20;30(36):4524-32. doi: 10.1200/JCO.2011.41.0852. Epub 2012 Oct 22.

  PMID: 23091097 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Chlorambucil; Cyclophosphamide; Doxorubicin; fludarabine phosphate; Prednisolone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Daniel Catovsky, MD

  Royal Marsden NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 28, 2000
• First Posted: January 27, 2003
• Study Start: October 1, 1999
• Study Completion: July 1, 2007
• Last Updated: December 18, 2013

Record last verified: 2006-01

Locations

CR (1); IT (1); NZ (1); RU (1); AR (2); GR (2); IE (2); GB (76)