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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00608374
First received: December 21, 2007
Last updated: August 23, 2013
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: chlorambucil
Drug: fludarabine phosphate
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Trial of Chlorambucil Versus Fludarabine as Initial Therapy of Waldenström's Macroglobulinaemia and Splenic Lymphoma With Villous Lymphocytes

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response to therapy (complete and partial response rates) [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement in hematological parameters [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire [ Designated as safety issue: No ]
  • Survival [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: June 2006
Study Completion Date: January 2013
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608374

  Hide Study Locations
Locations
Australia, Australian Capital Territory
Canberra Hospital
Garran, Australian Capital Territory, Australia, 2605
Australia, New South Wales
Newcastle Mater Misericordiae Hospital
Waratah, New South Wales, Australia, 2298
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Australia, South Australia
Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
United Kingdom
Stoke Mandeville Hospital
Aylesbury-Buckinghamshire, England, United Kingdom, HP21 8AL
North Devon District Hospital
Barnstaple, England, United Kingdom, EX31 4JB
Basingstoke and North Hampshire NHS Foundation Trust
Basingstoke, England, United Kingdom, RG24 9NA
Royal United Hospital
Bath, England, United Kingdom, BA1 3NG
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
City Hospital - Birmingham
Birmingham, England, United Kingdom, B18 7QH
Blackpool Victoria Hospital
Blackpool, England, United Kingdom, FY3 8NR
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom, BH7 7DW
Bradford Royal Infirmary
Bradford, England, United Kingdom, BD9 6RJ
Queen's Hospital
Burton-upon-Trent, England, United Kingdom, DE13 0RB
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, United Kingdom, GL53 7AN
Saint Richards Hospital
Chichester, England, United Kingdom, P019 4SE
Doncaster Royal Infirmary
Doncaster, England, United Kingdom, DN2 5LT
Russells Hall Hospital
Dudley, England, United Kingdom, DY1 2HQ
Royal Devon and Exeter Hospital
Exeter, England, United Kingdom, EX2 5DW
Gloucestershire Royal Hospital
Gloucester, England, United Kingdom, GL1 3NN
Harrogate District Hospital
Harrogate, England, United Kingdom, HG2 7SX
Hereford Hospitals
Hereford, England, United Kingdom, HR1 2ER
Watford General Hospital
Herts, England, United Kingdom, WD18 0HB
Wycombe General Hospital
High Wycombe, England, United Kingdom
Hull Royal Infirmary
Hull, England, United Kingdom, HU3 2KZ
Queen Elizabeth Hospital
King's Lynn, England, United Kingdom, PE30 4ET
Leeds General Infirmary
Leeds, England, United Kingdom, LS1 3EX
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
University College Hospital - London
London, England, United Kingdom, WC1E 6AU
Trafford General Hospital
Manchester, England, United Kingdom, M31 3SL
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Derriford Hospital
Plymouth, England, United Kingdom, PL6 8DH
Pontefract General Infirmary
Pontefract West Yorkshire, England, United Kingdom, WF8 1PL
Berkshire Cancer Centre at Royal Berkshire Hospital
Reading, England, United Kingdom, RG1 5AN
Rotherham General Hospital
Rotherham, England, United Kingdom, S60 2UD
Wexham Park Hospital
Slough, Berkshire, England, United Kingdom, SL2 4HL
Staffordshire General Hospital
Stafford, England, United Kingdom, ST16 3SA
Taunton and Somerset Hospital
Taunton Somerset, England, United Kingdom, TA1 5DA
Torbay Hospital
Torquay, England, United Kingdom, TQ2 7AA
Royal Cornwall Hospital
Truro, Cornwall, England, United Kingdom, TR1 3LJ
Kent and Sussex Hospital
Tunbridge Wells, Kent, England, United Kingdom, TN4 8AT
Sandwell General Hospital
West Bromwich, England, United Kingdom, B71 4HJ
New Cross Hospital
Wolverhampton, England, United Kingdom, WV10 0QP
Monklands General Hospital
Airdrie, Scotland, United Kingdom, ML6 0JF
Southern General Hospital
Glasgow, Scotland, United Kingdom, G51 4TF
Pinderfields General Hospital
Wakefield, Scotland, United Kingdom, WF1 4DG
Ysbyty Gwynedd
Bangor, Wales, United Kingdom, LL57 2PW
Sponsors and Collaborators
Taunton and Somerset Hospital
Investigators
Study Chair: Roger G. Owen, MD, MRCP Leeds Cancer Centre at St. James's University Hospital
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00608374     History of Changes
Other Study ID Numbers: CDR0000581143, TSH-WM1, ISRCTN56052618
Study First Received: December 21, 2007
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Lymphoma
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Chlorambucil
Fludarabine
Fludarabine monophosphate
Vidarabine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on July 26, 2014