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

August 23, 2013 updated by: Taunton and Somerset Hospital

A Randomised Trial of Chlorambucil Versus Fludarabine as Initial Therapy of Waldenström's Macroglobulinaemia and Splenic Lymphoma With Villous Lymphocytes

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.

Study Overview

Status

Completed

Conditions

Lymphoma

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Duration of response
Response to therapy (complete and partial response rates)

Secondary Outcome Measures

Outcome Measure
Toxicity
Survival
Improvement in hematological parameters
Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taunton and Somerset Hospital

Investigators

Study Chair: Roger G. Owen, MD, MRCP, Leeds Cancer Centre at St. James's University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

December 21, 2007

First Submitted That Met QC Criteria

January 26, 2008

First Posted (Estimate)

February 6, 2008

Study Record Updates

Last Update Posted (Estimate)

August 26, 2013

Last Update Submitted That Met QC Criteria

August 23, 2013

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CDR0000581143
TSH-WM1
ISRCTN56052618

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.