With an annual incidence of 3/100,000 chronic lymphocytic leukaemia is the most common leukaemia in western countries. Pathogenetically and cytomorphologically CLL belongs to the group of low-grade non-Hodgkin's lymphomas. More than 90 % of the cases are derived from B-lymphocytes. MedDRA version: 14.0 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: MabThera®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
CAS Number: 174722-31
Current Sponsor code: RO 45-2294
Other descriptive name: n/a
Conce
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •B-CLL confirmed according to NCI Working Group criteria [1] •Binet stage C as well as Binet stage B requiring treatment All patients must fulfill the criteria of disease requiring treatment. Disease requiring treatment is defined as: •Binet stage C •Binet stage B plus at least one of the following signs or symptoms: - B symptoms (night sweats, weight loss > or = 10% within the previous 6 months, fevers > 38°C or 100.4°F for > or = 2 weeks without evidence of infection) or constitutional symptoms (fatigue) - Continuous progression (doubling of peripheral lymphocyte count 50 G/l) - evidence of progressive marrow failure as manifested by the development / worsening of anemia and/or thrombocytopenia - massive, progressive or painful splenomegaly or hypersplenism - massive lymph nodes or lymph node clusters (> 10 cm in longest diameter), danger of organ complications through large lymphomas (e.g. vascular compression, e.g. tracheal narrowing) or progressive lymphadenopathy - Occurrence of symptomatic hyperviscosity problems at leucocyte counts > 200 G/l (symptomatic leucostasis) • No previous treatment of the CLL by chemotherapy, radiotherapy or immunotherapy. • Alkaline phosphatase and transaminases = 2 x ULN • A negative serum pregnancy test one week prior to treatment must be available both for pre-menopausal women and for women who are or = 18 years • Life expectancy > 6 months • ECOG performance status 0-1 • Patient's written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 567 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 243
Exclusion criteria
Exclusion criteria: • Stage Binet A • Clinically significant auto-immune cytopenia, Coombs-positive haemolytic anaemia as judged by the treating physician. • Active second malignancy currently requiring treatment (except basal cell carcinoma or tumour treated curatively by surgery) • Pregnancy,and/or nursing • Concomitant disease requiring prolonged use of glucocorticoids (> 1 month) • Known hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or any of the study drugs • CIRS score > 6 • Cerebral dysfunction which makes it impossible to perform chemotherapy • Transformation to aggressive B-cell malignancy (eg diffuse large cell lymphoma, Richter's syndrome, or prolymphocytic leukaemia) . • Active bacterial, viral or fungal infection. Although testing for hepatitis B is not mandatory, this should be considered for all patients considered at high risk of hepatitis B infection and in endemic areas. Patients with any serological evidence of current or past hepatitis B infection are excluded unless the serological findings are clearly due to vaccination. • Total bilirubin > 2 x ULN • Creatinine clearance < 70 ml/min calculated according to the formula of Cockcroft and Gault • Any coexisting medical or psychological condition that would preclude participation in the required study procedures. • Treatment with any other investigational agent, or participating in another clinical trial within 30 days prior to entering this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to determine the value of immunochemotherapy with FCR in comparison with chemotherapy with FC alone in the first-line therapy of B-CLL. The study is to answer the following questions: • Is combined immunochemotherapy with FCR superior in terms of progression free survival to chemotherapy with FC alone in the first-line therapy of B-CLL? • Is combined immunochemotherapy with FCR a safe alternative to FC chemotherapy alone with regards to the adverse effects? ;Secondary Objective: -Event-free survival -Overall survival -Disease-free survival -Duration of remission -Time to new CLL treatment or death -Rates of molecular, complete and partial remission -Response rates and survival times in biological subgroups -Rates of treatment-related adverse effects -Pharmacoeconomic impact -Quality of life ;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Median observation time at time of analysis was approximately 21 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Event-free Survival (EFS) 2. Overall Survival (OS) 3. Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR). ;Timepoint(s) of evaluation of this end point: Median observation time at time of analysis was approximately 21 months. | — |
Countries
Australia, Austria, Belgium, Czech Republic, Denmark, France, Germany, Israel, Italy, New Zealand, Spain
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed