Back to resultsPhase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma (MCLPIII)
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
rituximab
Cyclophosphamide
Fludarabine
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring 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
Eligibility 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
Sites / Locations
- Peter MacCallum Cancer Centre
- William Harvey Hospital
- Stoke Mandeville Hospital
- Basingstoke and North Hampshire NHS Foundation Trust
- Royal United Hospital
- Good Hope Hospital
- Birmingham Heartlands Hospital
- Blackpool Victoria Hospital
- Addenbrooke's Hospital
- Kent and Canterbury Hospital
- St. Helier Hospital
- Gloucestershire Oncology Centre at Cheltenham General Hospital
- Saint Richards Hospital
- Essex County Hospital
- Colchester General Hospital
- Queen Alexandra Hospital
- Mayday University Hospital
- Darlington Memorial
- Darent Valley Hospital
- Dewsbury and District Hospital
- Russells Hall Hospital
- Bishop Auckland Hospital
- Epsom General Hospital
- Royal Devon and Exeter Hospital
- Queen Elizabeth Hospital
- Medway Maritime Hospital
- Gloucestershire Royal Hospital
- Hereford Hospitals
- Wycombe General Hospital
- Leeds General Infirmary
- Cancer Research UK Clinical Centre at St. James's University Hospital
- Saint Bartholomew's Hospital
- Mid Kent Oncology Centre at Maidstone Hospital
- Manchester Royal Infirmary
- Christie Hospital
- Queen Elizabeth The Queen Mother Hospital
- Newcastle Upon Tyne Hospitals NHS Trust
- Mount Vernon Cancer Centre at Mount Vernon Hospital
- Norfolk and Norwich University Hospital
- Derriford Hospital
- Pontefract General Infirmary
- Portsmouth Oncology Centre at St Mary's Hospital
- Whiston Hospital
- Rosemere Cancer Centre at Royal Preston Hospital
- East Surrey Hospital
- Pembury Hospital
- Salisbury District Hospital
- Royal Hallamshire Hospital
- Cancer Research Centre at Weston Park Hospital
- Royal South Hants Hospital
- Southampton General Hospital
- Sunderland Royal Hospital
- Royal Marsden - Surrey
- Great Western Hospital
- Torbay Hospital
- Royal Cornwall Hospital
- Kent and Sussex Hospital
- New Cross Hospital
- Yeovil District Hospital
- Monklands General Hospital
- Hairmyres Hospital
- Raigmore Hospital
- Pinderfields General Hospital
- Wishaw General Hospital
- Ysbyty Gwynedd
- Amersham Hospital
- Musgrove Park Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fludarabine/Cyclophosphamide/Rituximab
Fludarabine/Cyclophosphamide
Arm Description
Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion Every 28 days
Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Every 28 days
Outcomes
Primary Outcome Measures
Overall survival
Overall survival - Time from date of first administration of treatment until death from any cause
Secondary Outcome Measures
Progression-free survival
Progression-free survival - Time from date of first administration of treatment to Disease Progression or replapse
Toxicity - Number of patients with >=grade 3 toxicity
Toxicity - Number of patients who suffer grade 3 or 4 toxicities
Toxicity - Percentage of patients with >=grade 3 toxicity
Toxicity - Percentage of patients who suffer grade 3 or 4 toxicities
Tumor response duration
Tumor response duration - Time from Complete or Partial Response to disease progression
Full Information
NCT ID
NCT00641095
First Posted
March 20, 2008
Last Updated
October 29, 2018
Sponsor
University College, London
Collaborators
Cancer Research UK
1. Study Identification
Unique Protocol Identification Number
NCT00641095
Brief Title
Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma
Acronym
MCLPIII
Official Title
Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
December 7, 2006 (Actual)
Primary Completion Date
November 23, 2011 (Actual)
Study Completion Date
May 22, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Cancer Research UK
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
370 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fludarabine/Cyclophosphamide/Rituximab
Arm Type
Experimental
Arm Description
Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion
Every 28 days
Arm Title
Fludarabine/Cyclophosphamide
Arm Type
Active Comparator
Arm Description
Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3
Every 28 days
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Description
concentrate for solution for infusion
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Tablets
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Film coated tablet
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival - Time from date of first administration of treatment until death from any cause
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
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Progression-free survival - Time from date of first administration of treatment to Disease Progression or replapse
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
Title
Toxicity - Number of patients with >=grade 3 toxicity
Description
Toxicity - Number of patients who suffer grade 3 or 4 toxicities
Time Frame
Within 30 days after last dose of treatment
Title
Toxicity - Percentage of patients with >=grade 3 toxicity
Description
Toxicity - Percentage of patients who suffer grade 3 or 4 toxicities
Time Frame
Within 30 days after last dose of treatment
Title
Tumor response duration
Description
Tumor response duration - Time from Complete or Partial Response to disease progression
Time Frame
From date of first documentation of PR or CR until the date of first progression up to a maximum of 60 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Simon Rule, MD
Organizational Affiliation
Derriford Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
William Harvey Hospital
City
Ashford
State/Province
England
ZIP/Postal Code
TN24 0LZ
Country
United Kingdom
Facility Name
Stoke Mandeville Hospital
City
Aylesbury
State/Province
England
ZIP/Postal Code
HP21 8AL
Country
United Kingdom
Facility Name
Basingstoke and North Hampshire NHS Foundation Trust
City
Basingstoke
State/Province
England
ZIP/Postal Code
RG24 9NA
Country
United Kingdom
Facility Name
Royal United Hospital
City
Bath
State/Province
England
ZIP/Postal Code
BA1 3NG
Country
United Kingdom
Facility Name
Good Hope Hospital
City
Birmingham
State/Province
England
ZIP/Postal Code
B75 7RR
Country
United Kingdom
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
State/Province
England
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Blackpool Victoria Hospital
City
Blackpool
State/Province
England
ZIP/Postal Code
FY3 8NR
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Kent and Canterbury Hospital
City
Canterbury
State/Province
England
ZIP/Postal Code
CT1 3NG
Country
United Kingdom
Facility Name
St. Helier Hospital
City
Carshalton
State/Province
England
ZIP/Postal Code
SM5 1AA
Country
United Kingdom
Facility Name
Gloucestershire Oncology Centre at Cheltenham General Hospital
City
Cheltenham
State/Province
England
ZIP/Postal Code
GL53 7AN
Country
United Kingdom
Facility Name
Saint Richards Hospital
City
Chichester
State/Province
England
ZIP/Postal Code
P019 4SE
Country
United Kingdom
Facility Name
Essex County Hospital
City
Colchester
State/Province
England
ZIP/Postal Code
C03 3NB
Country
United Kingdom
Facility Name
Colchester General Hospital
City
Colchester
State/Province
England
Country
United Kingdom
Facility Name
Queen Alexandra Hospital
City
Cosham
State/Province
England
ZIP/Postal Code
PO6 3LY
Country
United Kingdom
Facility Name
Mayday University Hospital
City
Croydon
State/Province
England
Country
United Kingdom
Facility Name
Darlington Memorial
City
Darlington
State/Province
England
ZIP/Postal Code
DL3 6HX
Country
United Kingdom
Facility Name
Darent Valley Hospital
City
Dartford
State/Province
England
ZIP/Postal Code
DA2 8DA
Country
United Kingdom
Facility Name
Dewsbury and District Hospital
City
Dewsbury
State/Province
England
ZIP/Postal Code
WF13 4HS
Country
United Kingdom
Facility Name
Russells Hall Hospital
City
Dudley
State/Province
England
ZIP/Postal Code
DY1 2HQ
Country
United Kingdom
Facility Name
Bishop Auckland Hospital
City
Durham
State/Province
England
Country
United Kingdom
Facility Name
Epsom General Hospital
City
Epsom
State/Province
England
ZIP/Postal Code
KT18 7EG
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
State/Province
England
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital
City
Gateshead
State/Province
England
ZIP/Postal Code
NE9 6SX
Country
United Kingdom
Facility Name
Medway Maritime Hospital
City
Gillingham
State/Province
England
ZIP/Postal Code
ME7 5NY
Country
United Kingdom
Facility Name
Gloucestershire Royal Hospital
City
Gloucester
State/Province
England
ZIP/Postal Code
GL1 3NN
Country
United Kingdom
Facility Name
Hereford Hospitals
City
Hereford
State/Province
England
ZIP/Postal Code
HR1 2ER
Country
United Kingdom
Facility Name
Wycombe General Hospital
City
High Wycombe
State/Province
England
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
State/Province
England
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Cancer Research UK Clinical Centre at St. James's University Hospital
City
Leeds
State/Province
England
ZIP/Postal Code
LS16 6QB
Country
United Kingdom
Facility Name
Saint Bartholomew's Hospital
City
London
State/Province
England
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
Mid Kent Oncology Centre at Maidstone Hospital
City
Maidstone
State/Province
England
ZIP/Postal Code
ME16 9QQ
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
State/Province
England
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Christie Hospital
City
Manchester
State/Province
England
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Queen Elizabeth The Queen Mother Hospital
City
Margate
State/Province
England
ZIP/Postal Code
CT9 4AN
Country
United Kingdom
Facility Name
Newcastle Upon Tyne Hospitals NHS Trust
City
Newcastle-Upon-Tyne
State/Province
England
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
Mount Vernon Cancer Centre at Mount Vernon Hospital
City
Northwood
State/Province
England
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
State/Province
England
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
State/Province
England
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Pontefract General Infirmary
City
Pontefract
State/Province
England
ZIP/Postal Code
WF8 1PL
Country
United Kingdom
Facility Name
Portsmouth Oncology Centre at St Mary's Hospital
City
Portsmouth
State/Province
England
ZIP/Postal Code
PO3 6AD
Country
United Kingdom
Facility Name
Whiston Hospital
City
Prescot
State/Province
England
ZIP/Postal Code
L35 5DR
Country
United Kingdom
Facility Name
Rosemere Cancer Centre at Royal Preston Hospital
City
Preston
State/Province
England
ZIP/Postal Code
PR2 9HT
Country
United Kingdom
Facility Name
East Surrey Hospital
City
Redhill
State/Province
England
ZIP/Postal Code
RH1 5RH
Country
United Kingdom
Facility Name
Pembury Hospital
City
Royal Tunbridge Wells
State/Province
England
ZIP/Postal Code
TN2 4QJ
Country
United Kingdom
Facility Name
Salisbury District Hospital
City
Salisbury
State/Province
England
ZIP/Postal Code
SP2 8BJ
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
State/Province
England
ZIP/Postal Code
S1O 2JF
Country
United Kingdom
Facility Name
Cancer Research Centre at Weston Park Hospital
City
Sheffield
State/Province
England
ZIP/Postal Code
S1O 2SJ
Country
United Kingdom
Facility Name
Royal South Hants Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO14 0YG
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Sunderland Royal Hospital
City
Sunderland
State/Province
England
ZIP/Postal Code
SR4 7TP
Country
United Kingdom
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Great Western Hospital
City
Swindon
State/Province
England
ZIP/Postal Code
SN3 6BB
Country
United Kingdom
Facility Name
Torbay Hospital
City
Torquay
State/Province
England
ZIP/Postal Code
TQ2 7AA
Country
United Kingdom
Facility Name
Royal Cornwall Hospital
City
Truro
State/Province
England
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
Facility Name
Kent and Sussex Hospital
City
Tunbridge Wells
State/Province
England
ZIP/Postal Code
TN4 8AT
Country
United Kingdom
Facility Name
New Cross Hospital
City
Wolverhampton
State/Province
England
ZIP/Postal Code
WV10 0QP
Country
United Kingdom
Facility Name
Yeovil District Hospital
City
Yeovil
State/Province
England
ZIP/Postal Code
BA21 4AT
Country
United Kingdom
Facility Name
Monklands General Hospital
City
Airdrie
State/Province
Scotland
ZIP/Postal Code
ML6 0JF
Country
United Kingdom
Facility Name
Hairmyres Hospital
City
East Kilbride
State/Province
Scotland
ZIP/Postal Code
G75 8RG
Country
United Kingdom
Facility Name
Raigmore Hospital
City
Inverness
State/Province
Scotland
ZIP/Postal Code
1V2 3UJ
Country
United Kingdom
Facility Name
Pinderfields General Hospital
City
Wakefield
State/Province
Scotland
ZIP/Postal Code
WF1 4DG
Country
United Kingdom
Facility Name
Wishaw General Hospital
City
Wishaw
State/Province
Scotland
ZIP/Postal Code
ML2 0DP
Country
United Kingdom
Facility Name
Ysbyty Gwynedd
City
Bangor
State/Province
Wales
ZIP/Postal Code
LL57 2PW
Country
United Kingdom
Facility Name
Amersham Hospital
City
Amersham
ZIP/Postal Code
HP7 0JD
Country
United Kingdom
Facility Name
Musgrove Park Hospital
City
Taunton
ZIP/Postal Code
TA1 5DA
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26611473
Citation
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.
Results Reference
derived
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/26611473
Description
Abstract on Pubmed
URL
http://www.haematologica.org/content/101/2/235.article-info
Description
Publication in haematologica
Learn more about this trial
Phase III, Multicentre, Randomised Study of Fludarabine/Cyclophosphamide Combination With or Without Rituximab in Patients With Untreated Mantle Cell Lymphoma
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