Chronic lymphocytic leukaemia (CLL) Cancer Lymphoid leukaemia
Conditions
Interventions
Patients will be randomised to receive 6 cycles of either FCR or FCM-miniR according to the following regimens:
Fludarabine, cyclophosphamide and rituximab (FCR):
Flud
Sponsors
Leeds Teaching Hospitals NHS Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Both males and females, at least 18 years old 2. B-CLL with a characteristic immunophenotype 3. Binet's Stages B, C or Progressive Stage A 4. Requiring therapy by the International Workshop on CLL (IWCLL) criteria in that they must have at least one of the following: 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 symptomatic lymphadenopathy 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. Unintentional weight loss more than or equal to 10% within the previous 6 months 8.2. Significant fatigue (i.e. Eastern Cooperative Oncology Group PS 2 or worse; cannot work or unable to perform usual activities) 8.3. Fevers of greater than 38.0°C for 2 or more weeks without other evidence of infection 8.4. Night sweats for more than 1 month without evidence of infection 9. No prior therapy for CLL 10. World Health Organization (WHO) performance status (PS) of 0, 1 or 2 11. Able to provide written informed consent
Exclusion criteria
Exclusion criteria: 1. Prior therapy for CLL 2. Active infection 3. Past history of anaphylaxis following exposure to rat or mouse derived 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 diseases or mental disorders 9. Known HIV positive 10. Patient has active or prior hepatitis B or C 11. Active secondary malignancy excluding basal cell carcinoma 12. Persisting severe pancytopenia (neutrophils <0.5 x 10^9/l or platelets <50 x 10^9/l) or transfusion dependent anaemia unless due to direct marrow infiltration by CLL 13. Active haemolysis (patients with haemolysis controlled with prednisolone at a dose 10 mg or less per day can be entered into the trial) 14. Patients with a creatinine clearance of less than 30 ml/min (either measured or derived by the Cockcroft formula)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients achieving a complete response (CR), as defined by the IWCLL criteria. A formal assessment of response by IWCLL criteria will be made 3 months after the end of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients with undetectable minimal residual disease (MRD) according to the IWCLL Response Criteria, assessed at baseline and 3 months after the end of therapy. Patients who are MRD negative at the end of treatment will also be followed up every 6 months after the end of therapy until disease progression requiring therapy or 2 years post-randomisation. All patients will be followed up for survival until death. 2. Overall response rate defined as complete or partial remission by IWCLL Criteria at 3 months after the end of therapy 3. Progression-free survival at 2 years 4. Overall survival at 2 years 5. Safety and toxicity. Adverse events (AEs) related to the treatment will be collected from randomisation until 30 days after the last dose of treatment with FCR or FCM-miniR. 6. Economic evaluation (time frame not yet finalised) | — |
Countries
England, Ireland, United Kingdom
Outcome results
None listed