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

Lymphoma Clinical Trial

— MCLPIII  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00641095
• Other study ID #: UCL/06/052
• Secondary ID: 2006-001965-41MR
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 7, 2006
• Est. completion date: May 22, 2015

Study information

• Verified date: October 2018
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: May 22, 2015
• Est. primary completion date: November 23, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Biological:
• rituximab
concentrate for solution for infusion

Drug:
• Cyclophosphamide
Tablets
• Fludarabine
Film coated tablet

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
United Kingdom	Monklands General Hospital	Airdrie	Scotland
United Kingdom	Amersham Hospital	Amersham
United Kingdom	William Harvey Hospital	Ashford	England
United Kingdom	Stoke Mandeville Hospital	Aylesbury	England
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Royal United Hospital	Bath	England
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Good Hope 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	St. Helier Hospital	Carshalton	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Saint Richards Hospital	Chichester	England
United Kingdom	Colchester General Hospital	Colchester	England
United Kingdom	Essex County Hospital	Colchester	England
United Kingdom	Queen Alexandra Hospital	Cosham	England
United Kingdom	Mayday University Hospital	Croydon	England
United Kingdom	Darlington Memorial	Darlington	England
United Kingdom	Darent Valley Hospital	Dartford	England
United Kingdom	Dewsbury and District Hospital	Dewsbury	England
United Kingdom	Russells Hall Hospital	Dudley	England
United Kingdom	Bishop Auckland Hospital	Durham	England
United Kingdom	Hairmyres Hospital	East Kilbride	Scotland
United Kingdom	Epsom General Hospital	Epsom	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	Medway Maritime Hospital	Gillingham	England
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	Hereford Hospitals	Hereford	England
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Raigmore Hospital	Inverness	Scotland
United Kingdom	Cancer Research UK Clinical Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leeds General Infirmary	Leeds	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Mid Kent Oncology Centre at Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Manchester Royal Infirmary	Manchester	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	England
United Kingdom	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Pontefract General Infirmary	Pontefract	England
United Kingdom	Portsmouth Oncology Centre at St Mary's Hospital	Portsmouth	England
United Kingdom	Whiston Hospital	Prescot	England
United Kingdom	Rosemere Cancer Centre at Royal Preston Hospital	Preston	England
United Kingdom	East Surrey Hospital	Redhill	England
United Kingdom	Pembury Hospital	Royal Tunbridge Wells	England
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Royal Hallamshire Hospital	Sheffield	England
United Kingdom	Royal South Hants Hospital	Southampton	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Sunderland Royal Hospital	Sunderland	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Great Western Hospital	Swindon	England
United Kingdom	Musgrove Park Hospital	Taunton
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro	England
United Kingdom	Kent and Sussex Hospital	Tunbridge Wells	England
United Kingdom	Pinderfields General Hospital	Wakefield	Scotland
United Kingdom	Wishaw General Hospital	Wishaw	Scotland
United Kingdom	New Cross Hospital	Wolverhampton	England
United Kingdom	Yeovil District Hospital	Yeovil	England

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK

Countries where clinical trial is conducted

Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival - Time from date of first administration of treatment until death from any cause	From date of first administration of treatment until the date of death from any cause, assessed up to a maximum of 60 months
Secondary	Progression-free survival	Progression-free survival - Time from date of first administration of treatment to Disease Progression or replapse	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
Secondary	Toxicity - Number of patients with >=grade 3 toxicity	Toxicity - Number of patients who suffer grade 3 or 4 toxicities	Within 30 days after last dose of treatment
Secondary	Toxicity - Percentage of patients with >=grade 3 toxicity	Toxicity - Percentage of patients who suffer grade 3 or 4 toxicities	Within 30 days after last dose of treatment
Secondary	Tumor response duration	Tumor response duration - Time from Complete or Partial Response to disease progression	From date of first documentation of PR or CR until the date of first progression up to a maximum of 60 months

External Links

•   Abstract on Pubmed
•   Publication in haematologica