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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

Tracking Information
First Submitted Date  ICMJE March 20, 2008
First Posted Date  ICMJE March 21, 2008
Last Update Posted Date October 31, 2018
Actual Study Start Date  ICMJE December 7, 2006
Actual Primary Completion Date November 23, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 20, 2008)
Overall survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2018)
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2008)
  • Progression-free survival
  • Toxicity
  • Tumor response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma
Official Title  ICMJE Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma
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.
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Biological: rituximab
    concentrate for solution for infusion
  • Drug: Cyclophosphamide
    Tablets
  • Drug: Fludarabine
    Film coated tablet
Study Arms  ICMJE
  • 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

    Interventions:
    • Biological: rituximab
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
  • Active Comparator: Fludarabine/Cyclophosphamide

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

    Every 28 days

    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
Publications * Rule S, Smith P, Johnson PW, Bolam S, Follows G, Gambell J, Hillmen P, Jack A, Johnson S, Kirkwood AA, Kruger A, Pocock C, Seymour JF, Toncheva M, Walewski J, Linch D. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. Haematologica. 2016 Feb;101(2):235-40. doi: 10.3324/haematol.2015.128710. Epub 2015 Nov 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 29, 2018)
370
Original Enrollment  ICMJE
 (submitted: March 20, 2008)
550
Actual Study Completion Date  ICMJE May 22, 2015
Actual Primary Completion Date November 23, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00641095
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University College, London
Study Sponsor  ICMJE University College, London
Collaborators  ICMJE Cancer Research UK
Investigators  ICMJE
Principal Investigator: Simon Rule, MD Derriford Hospital
PRS Account University College, London
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP