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

NCT ID: NCT00641095

Last Updated: 2018-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-12-07

Study Completion Date

2015-05-22

Brief Summary

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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

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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

Conditions

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Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

concentrate for solution for infusion

Cyclophosphamide

Intervention Type DRUG

Tablets

Fludarabine

Intervention Type DRUG

Film coated tablet

Fludarabine/Cyclophosphamide

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

Every 28 days

Group Type ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type DRUG

Tablets

Fludarabine

Intervention Type DRUG

Film coated tablet

Interventions

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rituximab

concentrate for solution for infusion

Intervention Type BIOLOGICAL

Cyclophosphamide

Tablets

Intervention Type DRUG

Fludarabine

Film coated tablet

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Simon Rule, MD

Role: PRINCIPAL_INVESTIGATOR

Derriford Hospital

Locations

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Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Site Status

William Harvey Hospital

Ashford, England, United Kingdom

Site Status

Stoke Mandeville Hospital

Aylesbury, England, United Kingdom

Site Status

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, United Kingdom

Site Status

Royal United Hospital

Bath, England, United Kingdom

Site Status

Good Hope Hospital

Birmingham, England, United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

Site Status

Blackpool Victoria Hospital

Blackpool, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Site Status

St. Helier Hospital

Carshalton, England, United Kingdom

Site Status

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, United Kingdom

Site Status

Saint Richards Hospital

Chichester, England, United Kingdom

Site Status

Essex County Hospital

Colchester, England, United Kingdom

Site Status

Colchester General Hospital

Colchester, England, United Kingdom

Site Status

Queen Alexandra Hospital

Cosham, England, United Kingdom

Site Status

Mayday University Hospital

Croydon, England, United Kingdom

Site Status

Darlington Memorial

Darlington, England, United Kingdom

Site Status

Darent Valley Hospital

Dartford, England, United Kingdom

Site Status

Dewsbury and District Hospital

Dewsbury, England, United Kingdom

Site Status

Russells Hall Hospital

Dudley, England, United Kingdom

Site Status

Bishop Auckland Hospital

Durham, England, United Kingdom

Site Status

Epsom General Hospital

Epsom, England, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

Site Status

Queen Elizabeth Hospital

Gateshead, England, United Kingdom

Site Status

Medway Maritime Hospital

Gillingham, England, United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, England, United Kingdom

Site Status

Hereford Hospitals

Hereford, England, United Kingdom

Site Status

Wycombe General Hospital

High Wycombe, England, United Kingdom

Site Status

Leeds General Infirmary

Leeds, England, United Kingdom

Site Status

Cancer Research UK Clinical Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Saint Bartholomew's Hospital

London, England, United Kingdom

Site Status

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, United Kingdom

Site Status

Manchester Royal Infirmary

Manchester, England, United Kingdom

Site Status

Christie Hospital

Manchester, England, United Kingdom

Site Status

Queen Elizabeth The Queen Mother Hospital

Margate, England, United Kingdom

Site Status

Newcastle Upon Tyne Hospitals NHS Trust

Newcastle upon Tyne, England, United Kingdom

Site Status

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, England, United Kingdom

Site Status

Derriford Hospital

Plymouth, England, United Kingdom

Site Status

Pontefract General Infirmary

Pontefract, England, United Kingdom

Site Status

Portsmouth Oncology Centre at St Mary's Hospital

Portsmouth, England, United Kingdom

Site Status

Whiston Hospital

Prescot, England, United Kingdom

Site Status

Rosemere Cancer Centre at Royal Preston Hospital

Preston, England, United Kingdom

Site Status

East Surrey Hospital

Redhill, England, United Kingdom

Site Status

Pembury Hospital

Royal Tunbridge Wells, England, United Kingdom

Site Status

Kent and Sussex Hospital

Royal Tunbridge Wells, England, United Kingdom

Site Status

Salisbury District Hospital

Salisbury, England, United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, England, United Kingdom

Site Status

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom

Site Status

Royal South Hants Hospital

Southampton, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Sunderland Royal Hospital

Sunderland, England, United Kingdom

Site Status

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status

Great Western Hospital

Swindon, England, United Kingdom

Site Status

Torbay Hospital

Torquay, England, United Kingdom

Site Status

Royal Cornwall Hospital

Truro, England, United Kingdom

Site Status

New Cross Hospital

Wolverhampton, England, United Kingdom

Site Status

Yeovil District Hospital

Yeovil, England, United Kingdom

Site Status

Monklands General Hospital

Airdrie, Scotland, United Kingdom

Site Status

Hairmyres Hospital

East Kilbride, Scotland, United Kingdom

Site Status

Raigmore Hospital

Inverness, Scotland, United Kingdom

Site Status

Pinderfields General Hospital

Wakefield, Scotland, United Kingdom

Site Status

Wishaw General Hospital

Wishaw, Scotland, United Kingdom

Site Status

Ysbyty Gwynedd

Bangor, Wales, United Kingdom

Site Status

Amersham Hospital

Amersham, , United Kingdom

Site Status

Musgrove Park Hospital

Taunton, , United Kingdom

Site Status

Countries

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Australia United Kingdom

References

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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.

Reference Type DERIVED
PMID: 26611473 (View on PubMed)

Related Links

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Other Identifiers

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2006-001965-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MREC-02/6/31

Identifier Type: OTHER

Identifier Source: secondary_id

ISRCTN

Identifier Type: REGISTRY

Identifier Source: secondary_id

UCL/06/052

Identifier Type: -

Identifier Source: org_study_id

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