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LymphomaPhase 2/3MCLPIIINCT00641095

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

A Phase 2/3 study testing rituximab, Cyclophosphamide and Fludarabine in people with Lymphoma, run by University College, London at 67 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Lymphoma
What is being tested?
rituximab, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
370 participants
Where
67 sitesin 2 countries
Study dates
7 Dec 2006to 22 May 2015
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

67 sites in 2 countries.

67 sites in 2 countries

United Kingdom66 sites

  • Monklands General Hospital

    Airdrie, Scotland, ML6 0JF

  • Amersham Hospital

    Amersham, HP7 0JD

  • William Harvey Hospital

    Ashford, England, TN24 0LZ

  • Stoke Mandeville Hospital

    Aylesbury, England, HP21 8AL

  • Ysbyty Gwynedd

    Bangor, Wales, LL57 2PW

  • Basingstoke and North Hampshire NHS Foundation Trust

    Basingstoke, England, RG24 9NA

  • Royal United Hospital

    Bath, England, BA1 3NG

  • Good Hope Hospital

    Birmingham, England, B75 7RR

  • Birmingham Heartlands Hospital

    Birmingham, England, B9 5SS

  • Blackpool Victoria Hospital

    Blackpool, England, FY3 8NR

  • Addenbrooke's Hospital

    Cambridge, England, CB2 2QQ

  • Kent and Canterbury Hospital

    Canterbury, England, CT1 3NG

  • St. Helier Hospital

    Carshalton, England, SM5 1AA

  • Gloucestershire Oncology Centre at Cheltenham General Hospital

    Cheltenham, England, GL53 7AN

  • Saint Richards Hospital

    Chichester, England, P019 4SE

  • Essex County Hospital

    Colchester, England, C03 3NB

  • Colchester General Hospital

    Colchester, England

  • Queen Alexandra Hospital

    Cosham, England, PO6 3LY

  • Mayday University Hospital

    Croydon, England

  • Darlington Memorial

    Darlington, England, DL3 6HX

  • Darent Valley Hospital

    Dartford, England, DA2 8DA

  • Dewsbury and District Hospital

    Dewsbury, England, WF13 4HS

  • Russells Hall Hospital

    Dudley, England, DY1 2HQ

  • Bishop Auckland Hospital

    Durham, England

  • Hairmyres Hospital

    East Kilbride, Scotland, G75 8RG

  • Epsom General Hospital

    Epsom, England, KT18 7EG

  • Royal Devon and Exeter Hospital

    Exeter, England, EX2 5DW

  • Queen Elizabeth Hospital

    Gateshead, England, NE9 6SX

  • Medway Maritime Hospital

    Gillingham, England, ME7 5NY

  • Gloucestershire Royal Hospital

    Gloucester, England, GL1 3NN

  • Hereford Hospitals

    Hereford, England, HR1 2ER

  • Wycombe General Hospital

    High Wycombe, England

  • Raigmore Hospital

    Inverness, Scotland, 1V2 3UJ

  • Leeds General Infirmary

    Leeds, England, LS1 3EX

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

    Leeds, England, LS16 6QB

  • Saint Bartholomew's Hospital

    London, England, EC1A 7BE

  • Mid Kent Oncology Centre at Maidstone Hospital

    Maidstone, England, ME16 9QQ

  • Manchester Royal Infirmary

    Manchester, England, M13 9WL

  • Christie Hospital

    Manchester, England, M20 4BX

  • Queen Elizabeth The Queen Mother Hospital

    Margate, England, CT9 4AN

  • Newcastle Upon Tyne Hospitals NHS Trust

    Newcastle upon Tyne, England, NE7 7DN

  • Mount Vernon Cancer Centre at Mount Vernon Hospital

    Northwood, England, HA6 2RN

  • Norfolk and Norwich University Hospital

    Norwich, England, NR4 7UY

  • Derriford Hospital

    Plymouth, England, PL6 8DH

  • Pontefract General Infirmary

    Pontefract, England, WF8 1PL

  • Portsmouth Oncology Centre at St Mary's Hospital

    Portsmouth, England, PO3 6AD

  • Whiston Hospital

    Prescot, England, L35 5DR

  • Rosemere Cancer Centre at Royal Preston Hospital

    Preston, England, PR2 9HT

  • East Surrey Hospital

    Redhill, England, RH1 5RH

  • Pembury Hospital

    Royal Tunbridge Wells, England, TN2 4QJ

  • Kent and Sussex Hospital

    Royal Tunbridge Wells, England, TN4 8AT

  • Salisbury District Hospital

    Salisbury, England, SP2 8BJ

  • Royal Hallamshire Hospital

    Sheffield, England, S1O 2JF

  • Cancer Research Centre at Weston Park Hospital

    Sheffield, England, S1O 2SJ

  • Royal South Hants Hospital

    Southampton, England, SO14 0YG

  • Southampton General Hospital

    Southampton, England, SO16 6YD

  • Sunderland Royal Hospital

    Sunderland, England, SR4 7TP

  • Royal Marsden - Surrey

    Sutton, England, SM2 5PT

  • Great Western Hospital

    Swindon, England, SN3 6BB

  • Musgrove Park Hospital

    Taunton, TA1 5DA

  • Torbay Hospital

    Torquay, England, TQ2 7AA

  • Royal Cornwall Hospital

    Truro, England, TR1 3LJ

  • Pinderfields General Hospital

    Wakefield, Scotland, WF1 4DG

  • Wishaw General Hospital

    Wishaw, Scotland, ML2 0DP

  • New Cross Hospital

    Wolverhampton, England, WV10 0QP

  • Yeovil District Hospital

    Yeovil, England, BA21 4AT

Other trials in United Kingdom

Australia1 site

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 3002

Other trials in Australia

About this study

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.

Read the 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

Conditions
Lymphoma
Keywords
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
Medical subject headings
Lymphoma, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00641095
Study groupRoleWhat they receive
Fludarabine/Cyclophosphamide/RituximabExperimentalFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion Every 28 days
Receives: Biological: rituximab; Drug: Cyclophosphamide; Drug: Fludarabine
Fludarabine/CyclophosphamideActive comparatorFludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Every 28 days
Receives: Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Overall survival - Time from date of first administration of treatment until death from any cause

    Measured: From date of first administration of treatment until the date of death from any cause, assessed up to a maximum of 60 months

Secondary outcomes (4)

  1. Progression-free survival

    Progression-free survival - Time from date of first administration of treatment to Disease Progression or replapse

    Measured: 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

  2. Toxicity - Number of patients with >=grade 3 toxicity

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

    Measured: Within 30 days after last dose of treatment

  3. Toxicity - Percentage of patients with >=grade 3 toxicity

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

    Measured: Within 30 days after last dose of treatment

  4. Tumor response duration

    Tumor response duration - Time from Complete or Partial Response to disease progression

    Measured: From date of first documentation of PR or CR until the date of first progression up to a maximum of 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2008 (estimated)
  2. Study start7 Dec 2006
  3. Primary completion23 Nov 2011
  4. Study completion22 May 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
370 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00641095
Sponsor's protocol ID
UCL/06/052
Other IDs
2006-001965-41, MREC-02/6/31, ISRCTN
Acronym
MCLPIII
Status last verified
Oct 2018
First submitted
20 Mar 2008
Last updated
31 Oct 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

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.

    PubMed 26611473

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing rituximab, Cyclophosphamide and Fludarabine in people with Lymphoma, run by University College, London at 67 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in United Kingdom, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00641095, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2018.

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