ISRCTN - ISRCTN42165735: CLL6 (Roche): a randomised, phase II trial of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone in previously untreated chronic lymphocytic leukaemia

Plain English Summary

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

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 measure

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 (if study stopped)

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 type

Hospital/treatment centre

Website

http://www.leedsteachinghospitals.com

Funders

Funder type

Industry

Funder name

Roche

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