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

Phase 2
Completed
Conditions
Lymphoma
Interventions
Registration Number
NCT00641095
Lead Sponsor
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.

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
370
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fludarabine/Cyclophosphamide/RituximabrituximabFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion Every 28 days
Fludarabine/Cyclophosphamide/RituximabCyclophosphamideFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion Every 28 days
Fludarabine/Cyclophosphamide/RituximabFludarabineFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion Every 28 days
Fludarabine/CyclophosphamideCyclophosphamideFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Every 28 days
Fludarabine/CyclophosphamideFludarabineFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Every 28 days
Primary Outcome Measures
NameTimeMethod
Overall survivalFrom 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
NameTimeMethod
Progression-free survivalFrom 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 toxicityWithin 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 toxicityWithin 30 days after last dose of treatment

Toxicity - Percentage of patients who suffer grade 3 or 4 toxicities

Tumor response durationFrom 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

Trial Locations

Locations (67)

Peter MacCallum Cancer Centre

🇦🇺

East Melbourne, Victoria, Australia

William Harvey Hospital

🇬🇧

Ashford, England, United Kingdom

Stoke Mandeville Hospital

🇬🇧

Aylesbury, England, United Kingdom

Basingstoke and North Hampshire NHS Foundation Trust

🇬🇧

Basingstoke, England, United Kingdom

Royal United Hospital

🇬🇧

Bath, England, United Kingdom

Good Hope Hospital

🇬🇧

Birmingham, England, United Kingdom

Birmingham Heartlands Hospital

🇬🇧

Birmingham, England, United Kingdom

Blackpool Victoria Hospital

🇬🇧

Blackpool, England, United Kingdom

Addenbrooke's Hospital

🇬🇧

Cambridge, England, United Kingdom

Kent and Canterbury Hospital

🇬🇧

Canterbury, England, United Kingdom

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Peter MacCallum Cancer Centre
🇦🇺East Melbourne, Victoria, Australia

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