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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00608374
• Other study ID #: CDR0000581143
• Secondary ID: TSH-WM1ISRCTN560
• Status: Completed
• Phase: Phase 3
• First received: December 21, 2007
• Last updated: August 23, 2013
• Start date: June 2006
• Est. completion date: January 2013

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: January 2013
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• chlorambucil

• fludarabine phosphate

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Newcastle Mater Misericordiae Hospital	Waratah	New South Wales
Australia	Queen Elizabeth Hospital	Woodville	South Australia
United Kingdom	Monklands General Hospital	Airdrie	Scotland
United Kingdom	Stoke Mandeville Hospital	Aylesbury-Buckinghamshire	England
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Royal United Hospital	Bath	England
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	City Hospital - Birmingham	Birmingham	England
United Kingdom	Blackpool Victoria Hospital	Blackpool	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Bradford Royal Infirmary	Bradford	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Saint Richards Hospital	Chichester	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	Russells Hall Hospital	Dudley	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Southern General Hospital	Glasgow	Scotland
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	Harrogate District Hospital	Harrogate	England
United Kingdom	Hereford Hospitals	Hereford	England
United Kingdom	Watford General Hospital	Herts	England
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Hull Royal Infirmary	Hull	England
United Kingdom	Queen Elizabeth Hospital	King's Lynn	England
United Kingdom	Leeds General Infirmary	Leeds	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	University College Hospital - London	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Trafford General Hospital	Manchester	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Pontefract General Infirmary	Pontefract West Yorkshire	England
United Kingdom	Berkshire Cancer Centre at Royal Berkshire Hospital	Reading	England
United Kingdom	Rotherham General Hospital	Rotherham	England
United Kingdom	Wexham Park Hospital	Slough, Berkshire	England
United Kingdom	Staffordshire General Hospital	Stafford	England
United Kingdom	Taunton and Somerset Hospital	Taunton Somerset	England
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	Kent and Sussex Hospital	Tunbridge Wells, Kent	England
United Kingdom	Pinderfields General Hospital	Wakefield	Scotland
United Kingdom	Sandwell General Hospital	West Bromwich	England
United Kingdom	New Cross Hospital	Wolverhampton	England

Sponsors (1)

Lead Sponsor	Collaborator
Taunton and Somerset NHS Foundation Trust

Countries where clinical trial is conducted

Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to therapy (complete and partial response rates)			No
Primary	Duration of response			No
Secondary	Improvement in hematological parameters			No
Secondary	Toxicity			Yes
Secondary	Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire			No
Secondary	Survival			No