Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Prof Peter Hillmen


Contact details

Department of Haematology
Level 3
Bexley Wing
St. James's University Hospital
Beckett Street
United Kingdom
+44 (0)113 206 8513

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

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


CLL6 (Roche)

Study hypothesis

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

Leeds (West) Research Ethics Committee, 09/02/2009, ref: 08/H1307/135

Study design

Phase II multi-centre randomised controlled open parallel-group trial

Primary study design


Secondary study design

Randomised parallel trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Chronic lymphocytic leukaemia (CLL)


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



Phase II

Drug names

Fludarabine, cyclophosphamide, rituximab, mitoxantrone

Primary outcome measures

Proportion of patients achieving a complete response (CR) at three months post end-of-treatment as specified by the IWCLL criteria.

Secondary outcome measures

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

Overall trial start date


Overall trial end date


Reason abandoned


Participant 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

Participant type


Age group




Target number of participants


Participant 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)

Recruitment start date


Recruitment end date



Countries of recruitment

Ireland, United Kingdom

Trial participating centre

St. James's University Hospital
United Kingdom

Sponsor information


Leeds Teaching Hospitals NHS Trust (UK)

Sponsor details

Research & Development
Floor A/B - Old Site
Leeds General Infirmary
Great George Street
United Kingdom
+44 (0)113 392 6473

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Roche Products Limited (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes