E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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?
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E.2.2 | Secondary objectives of the trial |
- 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
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 10% within the previous 6 months, fevers > 38°C or 100.4°F for 2 weeks without evidence of infection) or constitutional symptoms (fatigue) - Continuous progression (doubling of peripheral lymphocyte count < 6 months AND absolute 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 < 2 years after the onset of menopause. • Willingness to use contraception for the entire duration of the treatment and 2 months thereafter • Patient's written informed consent • Age 18 years • Life expectancy > 6 months • ECOG performance status 0-1 • Patient's written informed consent
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined when 357 events (progression or death) have occured. This estimation is based on a median progression free survival of 40 months in patients receiving the FC combination. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 9 |