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Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma (MCLPIII)

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ClinicalTrials.gov Identifier: NCT00641095
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : October 31, 2018
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
University College, London

Brief Summary:
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 Phase 2 Phase 3

Detailed Description:

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.

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.

This trial follows on from the Phase II randomised study of fludarabine/cyclophosphamide combination with or without Rituximab in patients with untreated mantle cell lymphoma. ISRCTN number: NCT00053092

Peer Reviewed and Funded or Endorsed by Cancer Research UK


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 370 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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
Actual Study Start Date : December 7, 2006
Actual Primary Completion Date : November 23, 2011
Actual Study Completion Date : May 22, 2015


Arm Intervention/treatment
Experimental: Fludarabine/Cyclophosphamide/Rituximab

Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion

Every 28 days

Biological: rituximab
concentrate for solution for infusion

Drug: Cyclophosphamide
Tablets

Drug: Fludarabine
Film coated tablet

Active Comparator: Fludarabine/Cyclophosphamide

Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3

Every 28 days

Drug: Cyclophosphamide
Tablets

Drug: Fludarabine
Film coated tablet




Primary Outcome Measures :
  1. Overall survival [ Time Frame: From date of first administration of treatment until the date of death from any cause, assessed up to a maximum of 60 months ]
    Overall survival - Time from date of first administration of treatment until death from any cause


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From date of first treatment administration until the date of first documented progression or relapse, whichever came first, assessed up to a maximum of 60 months ]
    Progression-free survival - Time from date of first administration of treatment to Disease Progression or replapse

  2. Toxicity - Number of patients with >=grade 3 toxicity [ Time Frame: Within 30 days after last dose of treatment ]
    Toxicity - Number of patients who suffer grade 3 or 4 toxicities

  3. Toxicity - Percentage of patients with >=grade 3 toxicity [ Time Frame: Within 30 days after last dose of treatment ]
    Toxicity - Percentage of patients who suffer grade 3 or 4 toxicities

  4. Tumor response duration [ Time Frame: From date of first documentation of PR or CR until the date of first progression up to a maximum of 60 months ]
    Tumor response duration - Time from Complete or Partial Response to disease progression



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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 ClinicalTrials.gov identifier (NCT number): NCT00641095


  Show 67 Study Locations
Sponsors and Collaborators
University College, London
Cancer Research UK
Investigators
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Principal Investigator: Simon Rule, MD Derriford Hospital

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00641095     History of Changes
Other Study ID Numbers: UCL/06/052
2006-001965-41 ( EudraCT Number )
MREC-02/6/31 ( Other Identifier: South West Multi-centre Research Ethics Committee )
ISRCTN ( Registry Identifier: NCT00641095 )
First Posted: March 21, 2008    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University College, London:
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:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Vidarabine
Cyclophosphamide
Rituximab
Fludarabine
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
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents