CLL6 (Roche): a randomised, phase II trial of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone in previously untreated chronic lymphocytic leukaemia

ISRCTN ISRCTN42165735
DOI https://doi.org/10.1186/ISRCTN42165735
Secondary identifying numbers HM08/8625
Submission date
17/06/2008
Registration date
02/10/2008
Last edited
27/07/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/trials-search/a-trial-looking-at-treatment-for-people-with-newly-diagnosed-chronic-lymphocytic-leukaemia

Contact information

Prof Peter Hillmen
Scientific

Department of Haematology
Level 3, Bexley Wing
St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Phone +44 (0)113 206 8513
Email peter.hillmen@nhs.net

Study information

Study designPhase II multi-centre randomised controlled open parallel-group trial
Primary study designInterventional
Secondary study designRandomised parallel trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleCLL6 (Roche): a randomised, phase II trial of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone in previously untreated chronic lymphocytic leukaemia
Study acronymCLL6 (Roche)
Study objectivesThe trial is intended to compare the complete remission rates of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone (M) in patients with previously untreated chronic lymphocytic leukaemia.
Ethics approval(s)Leeds (West) Research Ethics Committee, 09/02/2009, ref: 08/H1307/135
Health condition(s) or problem(s) studiedChronic lymphocytic leukaemia (CLL)
InterventionThis trial aims to recruit 218 patients over 18 months. Patients will be randomised to receive six cycles of either FCR or FCM-R. Cycles of FCR and FCM-R are reported every 28 days for a total of six courses. Each cycle is repeated every 28 days. However treatment is administered during each cycle as per the following schedule:

Patients randomised to receive fludarabine, cyclophosphamide and rituximab (FCR) will receive:
Fludarabine (oral): 24 mg/m^2/day on days 1 to 5
Cyclophosphamide (oral): 150 mg/m^2/day on days 1 to 5
Rituximab (IV): 375 mg/m^2 on day 1 (cycle 1)
Rituximab (IV): 500 mg/m^2 on day 1 (cycle 2 to 6)

Patients randomised to receive fludarabine, cyclophosphamide, rituximab and mitoxantrone (FCM-R) will receive:
Fludarabine (oral): 24 mg/m^2/day on days 1 to 5
Cyclophosphamide (oral): 150 mg/m^2/day on days 1 to 5
Rituximab (IV): 375 mg/m^2 on day 1 (cycle 1)
Rituximab (IV): 500 mg/m^2 on day 1 (cycle 2 to 6)
Mitoxantrone (IV): 6 mg/m^2/day on day 1
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Fludarabine, cyclophosphamide, rituximab, mitoxantrone
Primary outcome measureProportion of patients achieving a complete response (CR) at three months post end-of-treatment as specified by the IWCLL criteria
Secondary outcome measures1. Proportion of patients with undetectable minimal residual disease, measured at three months post-end-of-treatment
2. Overall response rate defined as complete or partial remission by the IWCLL criteria, measured at three months post-end-of-treatment
3. Progression free survival at two years
4. Overall survival at two years
5. Safety and toxicity, measured at two years after randomisation
Overall study start date01/01/2009
Completion date01/07/2012

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants218
Total final enrolment215
Key inclusion criteria1. Both males and females, at least 18 years old
2. B-cell chronic lymphocytic leukaemia (B-CLL) with a characteristic immunophenotype
3. Binet's Stages B, C or Progressive A
4. Requirement for therapy as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria (must meet one of the following criteria: evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia)
5. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
6. Massive nodes (i.e. 10 cm in longest diameter) or progressive or sypmtomatic lymphodenopathy
7. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months as long as the lymphocyte count is over 30 x 10^9/L
8. A minimum of any one of the following disease-related symptoms must be present:
8.1. Unitentional weight loss more than or equal to 10% within the previous 6 months
8.2. Significant fatigue (i.e. Eastern Cooperative Oncology Group performance status 2 or worse; cannot work or unable to perform usual activities)
8.4. Fevers of greater than 38°C for two or more weeks without other evidence of infection
8.5. Night sweats for more than one month without evidence of infection
9. No prior therapy for CLL
10. Able to provide written informed consent
Key exclusion criteria1. Prior therapy for CLL
2. Active infection
3. Past history of anaphylaxis following exposure to rat or mouse derived complementarity-determining regions (CDR)-grafted humanised monoclonal antibodies
4. Pregnancy, lactation or women of child bearing potential unwilling to use medically approved contraception whilst receiving treatment
5. Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception during the study, unless they are surgically sterile
6. Central nervous system (CNS) involvement with CLL
7. Mantle cell lymphoma
8. Other severe, concurrent disease or mental disorders
9. Known human immunodeficiency virus (HIV) positive
10. Patient has active or prior hepatitis B or C
11. Active secondary malignancy excluding basal cell lymphoma
12. Persisting severe pancytopenia (neutrophils less than 0.5 x 10^9/L or platelets less than 50 x 10^9/L), trasfusion dependent anaemia and active haemolysis
13. Patients with a creatinine clearance of less than 30 ml/min (either measured or derived by the Cockroft formula)
Date of first enrolment01/06/2009
Date of final enrolment30/03/2012

Locations

Countries of recruitment

  • England
  • Ireland
  • United Kingdom

Study participating centre

St. James's University Hospital
Leeds
LS9 7TF
United Kingdom

Sponsor information

Leeds Teaching Hospitals NHS Trust (UK)
Hospital/treatment centre

Research & Development
Floor A/B - Old Site
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
England
United Kingdom

Phone +44 (0)113 392 6473
Email derek.norfolk@leedsth.nhs.uk
Website http://www.leedsteachinghospitals.com
ROR logo "ROR" https://ror.org/00v4dac24

Funders

Funder type

Industry

Roche
Government organisation / For-profit companies (industry)
Alternative name(s)
F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG, Roche Holding AG, Roche Holding Ltd, Roche Holding, Roche Holding A.G., Roche Holding, Limited, F. Hoffmann-La Roche & Co.
Location
Switzerland

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/10/2017 Yes No
Plain English results 27/07/2022 No Yes
HRA research summary 28/06/2023 No No

Editorial Notes

27/07/2022: Cancer Research UK plain English results summary link and total final enrolment added.
26/06/2017: Publication reference added.