Chlorambucil or Fludarabine as First-Line Therapy in Treating Patients With Previously Untreated Waldenström Macroglobulinemia, Splenic Lymphoma, or Lymphoplasmacytic Lymphoma

NCT ID: NCT00608374

Last Updated: 2013-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-30

Study Completion Date

2013-01-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as chlorambucil and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether chlorambucil is more effective than fludarabine in treating Waldenström macroglobulinemia, splenic lymphoma, or lymphoplasmacytic lymphoma.

PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared with fludarabine as first-line therapy in treating patients with previously untreated Waldenström macroglobulinemia, splenic lymphoma, or lymphoplasmacytic lymphoma.

Detailed Description

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OBJECTIVES:

* Compare the efficacy of first-line therapy comprising chlorambucil vs fludarabine phosphate in patients with previously untreated Waldenström macroglobulinemia, splenic lymphoma with villous lymphocytes, or non-IgM lymphoplasmacytic lymphoma.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Waldenström macroglobulinemia vs splenic lymphoma with villous lymphocytes vs non-IgM lymphoplasmacytic lymphoma). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral chlorambucil on days 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive fludarabine phosphate orally or IV on days 1-5. Treatment repeats every 28 days for 3-6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo quality of life assessment at baseline.

Conditions

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Lymphoma

Keywords

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Waldenström macroglobulinemia splenic marginal zone lymphoma stage I marginal zone lymphoma stage III marginal zone lymphoma stage IV marginal zone lymphoma contiguous stage II marginal zone lymphoma noncontiguous stage II marginal zone lymphoma

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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chlorambucil

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

quality-of-life assessment

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

PATIENT CHARACTERISTICS:

* Performance status 0-2
* Life expectancy \> 6 months
* Serum creatinine \< 200 mmol/L
* AST and ALT \< 2 times upper limit of normal
* Negative direct Coomb's test
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
* No severe or life-threatening cardiac, pulmonary, neurological, psychiatric, or metabolic disease
* No other concurrent malignancy
* No AIDS or AIDS-related complex
* No evidence of active hepatitis C infection

PRIOR CONCURRENT THERAPY:

* Prior plasmapheresis for control of clinically significant hyperviscosity allowed
* Prior splenectomy for SLVL allowed
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taunton and Somerset Hospital

OTHER

Sponsor Role lead

Principal Investigators

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Roger G. Owen, MD, MRCP

Role: STUDY_CHAIR

Leeds Cancer Centre at St. James's University Hospital

Locations

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Canberra Hospital

Garran, Australian Capital Territory, Australia

Site Status

Newcastle Mater Misericordiae Hospital

Waratah, New South Wales, Australia

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Princess Alexandra Hospital

Brisbane, Queensland, Australia

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Queen Elizabeth Hospital

Woodville, South Australia, Australia

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Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

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Stoke Mandeville Hospital

Aylesbury-Buckinghamshire, England, United Kingdom

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North Devon District Hospital

Barnstaple, England, United Kingdom

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Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, United Kingdom

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Royal United Hospital

Bath, England, United Kingdom

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City Hospital - Birmingham

Birmingham, England, United Kingdom

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Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

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Blackpool Victoria Hospital

Blackpool, England, United Kingdom

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Royal Bournemouth Hospital

Bournemouth, England, United Kingdom

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Bradford Royal Infirmary

Bradford, England, United Kingdom

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Queen's Hospital

Burton-on-Trent, England, United Kingdom

Site Status

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, United Kingdom

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Saint Richards Hospital

Chichester, England, United Kingdom

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Doncaster Royal Infirmary

Doncaster, England, United Kingdom

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Russells Hall Hospital

Dudley, England, United Kingdom

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Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

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Gloucestershire Royal Hospital

Gloucester, England, United Kingdom

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Harrogate District Hospital

Harrogate, England, United Kingdom

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Hereford Hospitals

Hereford, England, United Kingdom

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Watford General Hospital

Herts, England, United Kingdom

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Wycombe General Hospital

High Wycombe, England, United Kingdom

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Hull Royal Infirmary

Hull, England, United Kingdom

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Queen Elizabeth Hospital

Kings Lynn, England, United Kingdom

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Leeds General Infirmary

Leeds, England, United Kingdom

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Saint Bartholomew's Hospital

London, England, United Kingdom

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University College Hospital - London

London, England, United Kingdom

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Royal Manchester Children's Hospital

Manchester, England, United Kingdom

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Trafford General Hospital

Manchester, England, United Kingdom

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Oxford Radcliffe Hospital

Oxford, England, United Kingdom

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Derriford Hospital

Plymouth, England, United Kingdom

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Pontefract General Infirmary

Pontefract West Yorkshire, England, United Kingdom

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Berkshire Cancer Centre at Royal Berkshire Hospital

Reading, England, United Kingdom

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Rotherham General Hospital

Rotherham, England, United Kingdom

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Wexham Park Hospital

Slough, Berkshire, England, United Kingdom

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Staffordshire General Hospital

Stafford, England, United Kingdom

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Taunton and Somerset Hospital

Taunton Somerset, England, United Kingdom

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Torbay Hospital

Torquay, England, United Kingdom

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Royal Cornwall Hospital

Truro, Cornwall, England, United Kingdom

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Kent and Sussex Hospital

Tunbridge Wells, Kent, England, United Kingdom

Site Status

Sandwell General Hospital

West Bromwich, England, United Kingdom

Site Status

New Cross Hospital

Wolverhampton, England, United Kingdom

Site Status

Monklands General Hospital

Airdrie, Scotland, United Kingdom

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Southern General Hospital

Glasgow, Scotland, United Kingdom

Site Status

Pinderfields General Hospital

Wakefield, Scotland, United Kingdom

Site Status

Ysbyty Gwynedd

Bangor, Wales, United Kingdom

Site Status

Countries

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Australia United Kingdom

References

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Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi: 10.1200/JCO.2012.44.7920. Epub 2012 Dec 10.

Reference Type DERIVED
PMID: 23233721 (View on PubMed)

Nguyen-Khac F, Lambert J, Chapiro E, Grelier A, Mould S, Barin C, Daudignon A, Gachard N, Struski S, Henry C, Penther D, Mossafa H, Andrieux J, Eclache V, Bilhou-Nabera C, Luquet I, Terre C, Baranger L, Mugneret F, Chiesa J, Mozziconacci MJ, Callet-Bauchu E, Veronese L, Blons H, Owen R, Lejeune J, Chevret S, Merle-Beral H, Leblondon V; Groupe Francais d'Etude de la Leucemie Lymphoide Chronique et Maladie de Waldenstrom (GFCLL/MW); Groupe Ouest-Est d'etude des Leucemie Aigues et Autres Maladies du Sang (GOELAMS); Groupe d'Etude des Lymphomes de l'Adulte (GELA). Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia. Haematologica. 2013 Apr;98(4):649-54. doi: 10.3324/haematol.2012.070458. Epub 2012 Oct 12.

Reference Type DERIVED
PMID: 23065509 (View on PubMed)

Other Identifiers

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TSH-WM1

Identifier Type: -

Identifier Source: secondary_id

ISRCTN56052618

Identifier Type: -

Identifier Source: secondary_id

CDR0000581143

Identifier Type: -

Identifier Source: org_study_id