Clinical trial NCT00608374: Chlorambucil or Fludarabine as First-Line Therapy in Treating Patients With Previously Untreated Waldenström Macroglobulinemia, Splenic Lymphoma, or Lymphoplasmacytic Lymphoma
Official title: A Randomised Trial of Chlorambucil Versus Fludarabine as Initial Therapy of Waldenström's Macroglobulinaemia and Splenic Lymphoma With Villous Lymphocytes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-02-06
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Response to therapy (complete and partial response rates)
measure: Duration of response
Secondary outcomes:
measure: Improvement in hematological parameters
measure: Toxicity
measure: Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire
measure: Survival
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Waratah
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Woodville
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Aylesbury-Buckinghamshire
country: United Kingdom
facility: Stoke Mandeville Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Birmingham
country: United Kingdom
facility: City Hospital - Birmingham
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Chichester
country: United Kingdom
facility: Saint Richards Hospital
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
state: England
city: Hereford
country: United Kingdom
facility: Hereford Hospitals
state: England
city: Herts
country: United Kingdom
facility: Watford General Hospital
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: University College Hospital - London
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Manchester
country: United Kingdom
facility: Trafford General Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Pontefract West Yorkshire
country: United Kingdom
facility: Pontefract General Infirmary
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Rotherham
country: United Kingdom
facility: Rotherham General Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Taunton Somerset
country: United Kingdom
facility: Taunton and Somerset Hospital
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Tunbridge Wells, Kent
country: United Kingdom
facility: Kent and Sussex Hospital
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Airdrie
country: United Kingdom
facility: Monklands General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Southern General Hospital
state: Scotland
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
Study officials:
affiliation: Leeds Cancer Centre at St. James's University Hospital
name: Roger G. Owen, MD, MRCP
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.