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

NCT00608374 | Completed Phase 3

• 3 other identifiers: CDR0000581143TSH-WM1ISRCTN56052618
• Study Type: interventional
• Target: 400
• Locations: 2 countries
• Sites: 49

Brief Summary

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Response to therapy (complete and partial response rates)

• Duration of response

Secondary Outcomes (4)

• Improvement in hematological parameters

• Toxicity

• Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire

• Survival

Interventions

chlorambucil DRUG

fludarabine phosphate DRUG

quality-of-life assessment PROCEDURE

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of Waldenström macroglobulinemia, splenic lymphoma with villous lymphocytes (SLVL), or non-IgM lymphoplasmacytic lymphoma based on morphological and immunophenotypic criteria * Bone marrow should be assessed by two-color flow cytometry for the expression of the following antigens: * Surface Ig * CD19 * CD20 * CD5 * CD10 * CD23 * Previously untreated disease requiring therapeutic intervention (as judged by the primary physician), as indicated by ≥ 1 of the following: * Hemoglobin \< 10 g/dL * ANC \< 1.5 x 10\^9/L * Platelet count \< 150 x 10\^9/L * Clinical evidence of hyperviscosity in terms of neurological or ocular disturbance * Patients with disease detected by clonal cells alone are not eligible 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

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

Sponsors & Collaborators

• Taunton and Somerset Hospital: lead

Study Sites (49)

Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Newcastle Mater Misericordiae Hospital

Waratah, New South Wales, 2298, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Stoke Mandeville Hospital

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

Location

North Devon District Hospital

Barnstaple, England, EX31 4JB, United Kingdom

Location

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, RG24 9NA, United Kingdom

Location

Royal United Hospital

Bath, England, BA1 3NG, United Kingdom

Location

City Hospital - Birmingham

Birmingham, England, B18 7QH, 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 Royal Infirmary

Bradford, England, BD9 6RJ, United Kingdom

Location

Queen's Hospital

Burton-on-Trent, England, DE13 0RB, United Kingdom

Location

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Saint Richards Hospital

Chichester, England, P019 4SE, United Kingdom

Location

Doncaster Royal Infirmary

Doncaster, England, DN2 5LT, United Kingdom

Location

Russells Hall Hospital

Dudley, England, DY1 2HQ, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

Location

Gloucestershire Royal Hospital

Gloucester, England, GL1 3NN, United Kingdom

Location

Harrogate District Hospital

Harrogate, England, HG2 7SX, United Kingdom

Location

Hereford Hospitals

Hereford, England, HR1 2ER, United Kingdom

Location

Watford General Hospital

Herts, England, WD18 0HB, United Kingdom

Location

Wycombe General Hospital

High Wycombe, England, United Kingdom

Location

Hull Royal Infirmary

Hull, England, HU3 2KZ, United Kingdom

Location

Queen Elizabeth Hospital

Kings Lynn, England, PE30 4ET, United Kingdom

Location

Leeds General Infirmary

Leeds, England, LS1 3EX, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

University College Hospital - London

London, England, WC1E 6AU, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, England, M27 4HA, United Kingdom

Location

Trafford General Hospital

Manchester, England, M31 3SL, United Kingdom

Location

Oxford Radcliffe Hospital

Oxford, England, 0X3 9DU, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, 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

Rotherham General Hospital

Rotherham, England, S60 2UD, United Kingdom

Location

Wexham Park Hospital

Slough, Berkshire, England, SL2 4HL, United Kingdom

Location

Staffordshire General Hospital

Stafford, England, ST16 3SA, United Kingdom

Location

Taunton and Somerset Hospital

Taunton Somerset, England, TA1 5DA, United Kingdom

Location

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

Location

Royal Cornwall Hospital

Truro, Cornwall, England, TR1 3LJ, United Kingdom

Location

Kent and Sussex Hospital

Tunbridge Wells, Kent, England, TN4 8AT, United Kingdom

Location

Sandwell General Hospital

West Bromwich, England, B71 4HJ, United Kingdom

Location

New Cross Hospital

Wolverhampton, England, WV10 0QP, United Kingdom

Location

Monklands General Hospital

Airdrie, Scotland, ML6 0JF, United Kingdom

Location

Southern General Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Pinderfields General Hospital

Wakefield, Scotland, WF1 4DG, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 23233721 DERIVED

• 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.

  PMID: 23065509 DERIVED

MeSH Terms

Conditions

Lymphoma; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone

Interventions

Chlorambucil; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Study Officials

• Roger G. Owen, MD, MRCP

  Leeds Cancer Centre at St. James's University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: February 6, 2008
• Study Start: June 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2013
• Last Updated: August 26, 2013

Record last verified: 2009-06

Locations

GB (44); AU (5)