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
Protocol serial number	HM08/8625
Sponsor	Leeds Teaching Hospitals NHS Trust (UK)
Funder	Roche

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

Primary study design	Interventional
Study design	Phase II multi-centre randomised controlled open parallel-group trial
Secondary study design	Randomised parallel trial
Study type	Participant information sheet
Scientific title	CLL6 (Roche): a randomised, phase II trial of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone in previously untreated chronic lymphocytic leukaemia
Study acronym	CLL6 (Roche)
Study objectives	The 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) studied	Chronic lymphocytic leukaemia (CLL)
Intervention	This 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 type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Fludarabine, cyclophosphamide, rituximab, mitoxantrone
Primary outcome measure(s)	Proportion of patients achieving a complete response (CR) at three months post end-of-treatment as specified by the IWCLL criteria
Key secondary outcome measure(s)	1. 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
Completion date	01/07/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	218
Total final enrolment	215
Key inclusion criteria	1. 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 criteria	1. 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 enrolment	01/06/2009
Date of final enrolment	30/03/2012

Locations

Countries of recruitment

United Kingdom
England
Ireland

Study participating centre

St. James's University Hospital

Leeds
LS9 7TF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not 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
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			27/07/2022	No	Yes

Editorial Notes

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