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LeukemiaPhase 3NCT00004218

Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

A Phase 3 study testing chlorambucil, cyclophosphamide and doxorubicin hydrochloride in people with Leukemia, run by Leukemia Research Fund at 86 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any age
Conditions the study is for
Leukemia
What is being tested?
chlorambucil, cyclophosphamide and doxorubicin hydrochloride
How many people
Not given
Where
86 sitesin 8 countries
Study dates
Oct 1999to Jul 2007
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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

Trial locations and contacts

86 sites in 8 countries.

86 sites in 8 countries

United Kingdom76 sites

  • Aberdeen Royal Infirmary

    Aberdeen, Scotland, AB25 2ZN

  • Monklands General Hospital

    Airdrie, Scotland, ML6 0JF

  • Stoke Mandeville Hospital

    Aylesbury-Buckinghamshire, England, HP21 8AL

  • Horton Hospital

    Banbury, England, OX16 9A

  • Ysbyty Gwynedd

    Bangor, Wales, LL57 2PW

  • North Hampshire Hospital

    Basingstoke, England, RG24 9NA

  • Belfast City Hospital Trust

    Belfast, Northern Ireland, BT9 7AB

  • Selly Oak Hospital at University Hospital NHS Trust

    Birmingham, England, B29 6JD

  • Birmingham Heartlands Hospital

    Birmingham, England, B9 5SS

  • Blackpool Victoria Hospital

    Blackpool, England, FY3 8NR

  • Royal Bournemouth Hospital

    Bournemouth, England, BH7 7DW

  • Bradford Hospitals NHS Trust

    Bradford, England, BD9 6RJ

  • Royal Sussex County Hospital

    Brighton, England, BN2 5BE

  • Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

    Cambridge, England, CB2 2QQ

  • St Helier Hospital

    Carshalton, England, SM5 1AA

  • Countess of Chester Hospital

    Chester, England, CH2 1UL

  • Chesterfield Royal Hospital

    Chesterfield, England, S44 5BL

  • Saint Richards Hospital

    Chichester, England, P019 4SE

  • Darlington Memorial

    Darlington, England, DL3 6HX

  • Dartford & Gravesham NHS Trust, Joyce Green Hospital

    Dartford Kent, England, DA1 5PL

  • Doncaster Royal Infirmary

    Doncaster, England, DN2 5LT

  • Russells Hall Hospital

    Dudley, England, DY1 2HQ

  • Dumfries Royal Infirmary

    Dumfries, Scotland, DG1 4AP

  • Ulster Hospital

    Dundonald, Northern Ireland, BT16

  • Bishop Auckland Hospital

    Durham, England

  • Western General Hospital

    Edinburgh, Scotland, EH4 2XU

  • Epsom General Hospital

    Epsom Surrey, England, KT18 7E9

  • Queen Elizabeth Hospital

    Gateshead, England, NE9 6SX

  • Queen Elizabeth Hospital

    Gateshead-Tyne and Wear, England, NE9 6SX

  • Southern General Hospital

    Glasgow, Scotland, G51 4TF

  • Gloucester Royal NHS Trust - Glouchester Royal Hospital

    Gloucester, England, GL1 3NN

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

    Guildford, England, GU2 5XX

  • Nevill Hall Hospital

    Gwent, Wales

  • Harrogate District Hospital

    Harrogate, England, HG2 7SX

  • Hemel Hempstead General

    Hemel Hempstead, England

  • Institute of Oncology and Radiology of Serbia

    High Wycombe, England

  • Huddersfield Royal Infirmary

    Huddersfield, West Yorks, England, HD3 3EA

  • Hull Royal Infirmary

    Hull, England, HU3 2KZ

  • Raigmore Hospital

    Inverness, Scotland, 1V2 3UJ

  • Victoria Hospital

    Kirkcaldy, Scotland, KY2 5AH

  • Clinical Trials and Research Unit of the University of Leeds

    Leeds, England, LS2 9N9

  • Leicester Royal Infirmary

    Leicester, England, LE1 5WW

  • Royal Liverpool and Broadgreen Hospitals

    Liverpool, England, L7 8XP

  • Walton General Hospital

    Liverpool, England, L9 1AE

  • Aintree University Hospital

    Liverpool, England, L9 7AL

  • Whipps Cross Hospital

    London, England, E11 1NR

  • Royal Free and University College Medical School

    London, England, NW1 2QG

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

    London, England, SE1 9RT

  • St. George's Hospital

    London, England, SW17 0QT

  • Royal Marsden NHS Foundation Trust - London

    London, England, SW3 6JJ

  • West Middlesex Hospital

    Middlesex, England, N18 1QZ

  • Northern Cancer Network

    Newcastle upon Tyne, England, NE27 OQJ

  • Northampton General Hospital NHS Trust

    Northampton, England, NN1 5BD

  • Nottingham City Hospital NHS Trust

    Nottingham, England, NG5 1PB

  • Bassetlaw Hospital & Community Services NHS Trust

    Nottinghamshire, England, S81 3SA

  • Farnborough Hospital

    Orpington Kent, England, BR6 8ND

  • Wharfdale General Hospital

    Otley, England, LS21 7AA

  • Royal Alexandra Hospital

    Paisley, Scotland

  • Pontefract General Infirmary

    Pontefract West Yorkshire, England, WF8 1PL

  • Craigavon Area Hospital

    Portadown, Craigavon, Northern Ireland, BT63 5QQ

  • Berkshire Cancer Centre at Royal Berkshire Hospital

    Reading, England, RG1 5AN

  • Oldchurch Hospital

    Romford, England, RM7 OBE

  • Rotherham District General Hospital - NHS Trust

    Rotherham, England, S60 2UD

  • Conquest Hospital

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

  • Scunthorpe General Hospital

    Scunthorpe, England, DN15 7BH

  • Royal South Hants Hospital

    Southampton, England, SO14 0YG

  • Southampton General Hospital

    Southampton, England, SO16 6YD

  • Staffordshire General Hospital

    Stafford, England, ST16 3SA

  • North Staffs Royal Infirmary

    Stoke-on-Trent, England, ST4 7LN

  • St. Peter's Hospital NHS Trust

    Surrey, England, KT 16 OPZ

  • Singleton Hospital

    Swansea, Wales, SA 2 8QA

  • Torbay Hospital

    Torquay Devon, England, TQ2 7AA

  • City Hospital - Birmingham

    West Bromwich, England, B71 4HJ

  • Good Hope Hospital Trust

    West Midlands, England, B75 7RR

  • Worthing Hospital

    Worthing, England, BN11 2DH

  • Cancer Care Centre at York Hospital

    York, England, Y031 8HE

Other trials in United Kingdom

Argentina2 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires, CP1181ACH

  • Hospital Alvarez

    Buenos Aires

Other trials in Argentina

Greece2 sites

  • University of Ioannina

    Ioannina, GR-45110

  • University of Patras Medical School

    Rio Patras, GR-26500

Other trials in Greece

Ireland2 sites

  • St. James' Hospital

    Dublin, 8

  • Galway University Hospital

    Galway

Other trials in Ireland

Croatia1 site

  • University Hospital Rebro

    Zagreb, 10000

Other trials in Croatia

Italy1 site

  • Ospedali Riuniti di Bergamo

    Bergamo, 24100

Other trials in Italy

New Zealand1 site

  • Canterbury Health Laboratories

    Christchurch

Other trials in New Zealand

Russia1 site

  • Russian Academy of Medical Sciences Cancer Research Center

    Moscow, 115478

Other trials in Russia

About this study

Official title: Chronic Lymphocytic Leukemia Trial 4: A Randomized Comparison of Chlorambucil, Fludarabine and Fludarabine Plus Cyclophosphamide

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.

Read the detailed description

OBJECTIVES:

  • Compare the survival rate of patients with newly diagnosed chronic lymphocytic leukemia treated with chlorambucil alone vs fludarabine with or without cyclophosphamide.
  • Compare the response rate and duration of remission in patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.
  • Compare the quality of life of patients treated with these regimens.
  • Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients.
  • Assess the prognostic value of five genetic markers: trisomy 12 and deletions at 11q23, 13q14, p53, and 6q21 in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients enter one of three treatment arms in the first randomization. Depending on response, some patients may also participate in a second randomization to one of two treatment arms.

  • First randomization:
  • Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year.
  • Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.
  • Arm III: Patients receive cyclophosphamide IV and fludarabine IV for 3 days or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.

Patients who relapse after being in remission for at least 1 year may repeat the initial therapy or may participate in a second randomization. Patients who experience progressive disease or relapse within 1 year after treatment proceed to a second randomization.

  • Second randomization:
  • Arm I: Treatment is guided by the results of the DiSC assay. Treatment may be one of the first-line treatments with fludarabine or standard CHOP chemotherapy repeated every 4 weeks (cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisolone on days 1-5) or any other therapy guided by the results of the DiSC assay.
  • Arm II: Treatment is physician's choice, which may include any of the options in arm I.

Quality of life is assessed prior to initial therapy; at 3, 6, and 12 months; and then annually thereafter.

Patients are followed annually for survival.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study within 6-7 years.

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
Medical subject headings
Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startOct 1999
  3. Study completionJul 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004218
Sponsor's protocol ID
CDR0000067454
Other IDs
LRF-CLL4, LRG-MRC-LEUK-CLL4, EU-99030, MRC-LEUK-CLL4, EUDRACT-58585610, ISRCTN58585610
Status last verified
Jan 2006
First submitted
28 Jan 2000
Last updated
18 Dec 2013
Results posted
No

Publications

  • 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.

    PubMed 22168274

  • 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.

    PubMed 21483000

  • 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.

    PubMed 21659360

  • 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.

    PubMed 20511662

  • 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.

    PubMed 19016733

  • 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.

    PubMed 17658394

  • 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.

  • 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.

    PubMed 23091097

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing chlorambucil, cyclophosphamide and doxorubicin hydrochloride in people with Leukemia, run by Leukemia Research Fund at 86 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 86 sites in United Kingdom, Argentina, Greece, Ireland, Croatia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004218, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2013.

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