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

  Show 49 Study Locations
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 phosphate
Vidarabine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 28, 2014