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

NCT00641095 | Completed Phase 2 DMC

• 4 other identifiers: UCL/06/0522006-001965-41MREC-02/6/31ISRCTN
• Study Type: interventional
• Target: 370
• Locations: 2 countries
• Sites: 67

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Progression-free survival

  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

• Toxicity - Number of patients with >=grade 3 toxicity

  Within 30 days after last dose of treatment

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

  Within 30 days after last dose of treatment

• Tumor response duration

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

Study Arms (2)

Fludarabine/Cyclophosphamide/Rituximab

EXPERIMENTAL

Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Rituximab 375mgs/m2 day 1 iv infusion Every 28 days

Biological: rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

Fludarabine/Cyclophosphamide

ACTIVE COMPARATOR

Fludarabine 40mgs/m2 oral days 1-3 Cyclophosphamide 250mgs/m2 oral days 1-3 Every 28 days

Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

rituximab BIOLOGICAL

concentrate for solution for infusion

Fludarabine/Cyclophosphamide/Rituximab

Cyclophosphamide DRUG

Tablets

Fludarabine/Cyclophosphamide; Fludarabine/Cyclophosphamide/Rituximab

Fludarabine DRUG

Film coated tablet

Fludarabine/Cyclophosphamide; Fludarabine/Cyclophosphamide/Rituximab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator

Study Sites (67)

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

William Harvey Hospital

Ashford, England, TN24 0LZ, United Kingdom

Location

Stoke Mandeville Hospital

Aylesbury, England, HP21 8AL, United Kingdom

Location

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, RG24 9NA, United Kingdom

Location

Royal United Hospital

Bath, England, BA1 3NG, United Kingdom

Location

Good Hope Hospital

Birmingham, England, B75 7RR, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, England, FY3 8NR, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, England, CT1 3NG, United Kingdom

Location

St. Helier Hospital

Carshalton, England, SM5 1AA, United Kingdom

Location

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Saint Richards Hospital

Chichester, England, P019 4SE, United Kingdom

Location

Essex County Hospital

Colchester, England, C03 3NB, United Kingdom

Location

Colchester General Hospital

Colchester, England, United Kingdom

Location

Queen Alexandra Hospital

Cosham, England, PO6 3LY, United Kingdom

Location

Mayday University Hospital

Croydon, England, United Kingdom

Location

Darlington Memorial

Darlington, England, DL3 6HX, United Kingdom

Location

Darent Valley Hospital

Dartford, England, DA2 8DA, United Kingdom

Location

Dewsbury and District Hospital

Dewsbury, England, WF13 4HS, United Kingdom

Location

Russells Hall Hospital

Dudley, England, DY1 2HQ, United Kingdom

Location

Bishop Auckland Hospital

Durham, England, United Kingdom

Location

Epsom General Hospital

Epsom, England, KT18 7EG, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

Location

Queen Elizabeth Hospital

Gateshead, England, NE9 6SX, United Kingdom

Location

Medway Maritime Hospital

Gillingham, England, ME7 5NY, United Kingdom

Location

Gloucestershire Royal Hospital

Gloucester, England, GL1 3NN, United Kingdom

Location

Hereford Hospitals

Hereford, England, HR1 2ER, United Kingdom

Location

Wycombe General Hospital

High Wycombe, England, United Kingdom

Location

Leeds General Infirmary

Leeds, England, LS1 3EX, United Kingdom

Location

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

Leeds, England, LS16 6QB, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Queen Elizabeth The Queen Mother Hospital

Margate, England, CT9 4AN, United Kingdom

Location

Newcastle Upon Tyne Hospitals NHS Trust

Newcastle upon Tyne, England, NE7 7DN, United Kingdom

Location

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, HA6 2RN, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, England, NR4 7UY, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Pontefract General Infirmary

Pontefract, England, WF8 1PL, United Kingdom

Location

Portsmouth Oncology Centre at St Mary's Hospital

Portsmouth, England, PO3 6AD, United Kingdom

Location

Whiston Hospital

Prescot, England, L35 5DR, United Kingdom

Location

Rosemere Cancer Centre at Royal Preston Hospital

Preston, England, PR2 9HT, United Kingdom

Location

East Surrey Hospital

Redhill, England, RH1 5RH, United Kingdom

Location

Pembury Hospital

Royal Tunbridge Wells, England, TN2 4QJ, United Kingdom

Location

Kent and Sussex Hospital

Royal Tunbridge Wells, England, TN4 8AT, United Kingdom

Location

Salisbury District Hospital

Salisbury, England, SP2 8BJ, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, England, S1O 2JF, United Kingdom

Location

Cancer Research Centre at Weston Park Hospital

Sheffield, England, S1O 2SJ, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, England, SR4 7TP, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Great Western Hospital

Swindon, England, SN3 6BB, United Kingdom

Location

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

Location

Royal Cornwall Hospital

Truro, England, TR1 3LJ, United Kingdom

Location

New Cross Hospital

Wolverhampton, England, WV10 0QP, United Kingdom

Location

Yeovil District Hospital

Yeovil, England, BA21 4AT, United Kingdom

Location

Monklands General Hospital

Airdrie, Scotland, ML6 0JF, United Kingdom

Location

Hairmyres Hospital

East Kilbride, Scotland, G75 8RG, United Kingdom

Location

Raigmore Hospital

Inverness, Scotland, 1V2 3UJ, United Kingdom

Location

Pinderfields General Hospital

Wakefield, Scotland, WF1 4DG, United Kingdom

Location

Wishaw General Hospital

Wishaw, Scotland, ML2 0DP, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

Amersham Hospital

Amersham, HP7 0JD, United Kingdom

Location

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26611473 DERIVED

Related Links

• Abstract on Pubmed
• Publication in haematologica

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell

Interventions

Rituximab; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Simon Rule, MD

  Derriford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2008
• First Posted: March 21, 2008
• Study Start: December 7, 2006
• Primary Completion: November 23, 2011
• Study Completion: May 22, 2015
• Last Updated: October 31, 2018

Record last verified: 2018-10

Locations

AU (1); GB (66)