Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Prof Peter Hillmen
ORCID ID
Contact details
Department of Haematology
Level 3
Bexley Wing
St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
+44 (0)113 206 8513
peter.hillmen@nhs.net
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HM08/8625
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
Acronym
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
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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 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
01/01/2009
Overall trial end date
01/07/2012
Reason abandoned
Eligibility
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
Patient
Age group
Adult
Gender
Both
Target number of participants
218
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
01/06/2009
Recruitment end date
30/03/2012
Locations
Countries of recruitment
Ireland, United Kingdom
Trial participating centre
St. James's University Hospital
Leeds
LS9 7TF
United Kingdom
Sponsor information
Organisation
Leeds Teaching Hospitals NHS Trust (UK)
Sponsor details
Research & Development
Floor A/B - Old Site
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom
+44 (0)113 392 6473
derek.norfolk@leedsth.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Roche
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Switzerland
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
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28216660