Fludarabine and Cyclophosphamide With or Without Rituximab in Treating Patients With Previously Untreated Mantle Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00641095
Recruitment Status : Unknown
Verified November 2008 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : March 21, 2008
Last Update Posted : August 12, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving combination chemotherapy together with rituximab is more effective than combination chemotherapy alone in treating mantle cell lymphoma.

PURPOSE: This randomized phase III trial is comparing how well fludarabine and cyclophosphamide work when given together with or without rituximab in treating patients with previously untreated mantle cell lymphoma.

Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate Genetic: fluorescence in situ hybridization Other: immunohistochemistry staining method Other: immunologic technique Other: laboratory biomarker analysis Phase 3

Detailed Description:



  • To determine the overall survival in patients with untreated mantle cell lymphoma treated with fludarabine phosphate and cyclophosphamide with vs without rituximab.


  • To determine the progression-free survival in patients treated with this regimen.
  • To determine the toxicity of this regimen in these patients.
  • To determine the tumor response in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive fludarabine phosphate IV or orally once daily and oral cyclophosphamide once daily on days 1-3. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive rituximab IV on day 1 and fludarabine phosphate IV or orally once daily and oral cyclophosphamide once daily on days 1-3. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow and blood sample collection periodically for molecular studies. Samples are analyzed for morphology; sIgM, sIgD, CD19, CD20, CD5, CD10, CD23, bcl-1, bcl-6 via immunophenotyping and immunohistochemistry; and t(11,14) translocation via interphase fluorescence in situ hybridization (FISH) mutational analysis.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 550 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma
Study Start Date : December 2006
Estimated Primary Completion Date : September 2010

Primary Outcome Measures :
  1. Overall survival

Secondary Outcome Measures :
  1. Progression-free survival
  2. Toxicity
  3. Tumor response

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed mantle cell lymphoma (MCL), meeting the following criteria:

    • Diagnosis confirmed by examination of representative material (lymph nodes or bone marrow) together with a typical immunophenotype CD5+, CD23-, sIgM, cyclin D1 nuclear positivity is desirable but not essential
    • Central review of histology will be performed on diagnostic material
    • Molecular or cytogenetic confirmation of diagnosis is not required
  • Previously untreated disease at any stage requiring therapy in the opinion of the treating physician


  • Life expectancy ≥ 3 months

    • Life expectancy not severely limited by other illness
  • Creatinine clearance ≥ 30 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during study therapy
  • No known serological positivity for HBV, HCV, or HIV
  • No concurrent uncontrolled serious medical conditions
  • No severe impairment of renal or liver function (alkaline phosphatase, bilirubin or creatinine > 2.5 times upper limit of normal) not related to lymphoma
  • No known hypersensitivity to murine proteins
  • No prior malignancy in the past 5 years, except for nonmelanoma skin tumor or curatively resected carcinoma in situ of the uterine cervix
  • No history of a psychological illness or condition that, in the opinion of the investigator, may adversely affect compliance with study medication


  • No prior chemotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00641095

  Show 67 Study Locations
Sponsors and Collaborators
Derriford Hospital
Principal Investigator: Simon Rule, MD Derriford Hospital

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00641095     History of Changes
Other Study ID Numbers: CRUK-UCL-MCLIII
CDR0000589227 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: March 21, 2008    Key Record Dates
Last Update Posted: August 12, 2013
Last Verified: November 2008

Keywords provided by National Cancer Institute (NCI):
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents