E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic lymphocytic leukaemia (CLL) |
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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 |
1) A comparison of the effect of immediate versus deferred treatment with FCR in Binet stage A patients at high risk for disease progression on event free survival (EFS). 2) Investigation and definition of a new prognostic staging system for patients with Binet stage A. |
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E.2.2 | Secondary objectives of the trial |
Progression free survival (PFS) Time to progression to Binet stages B and C Time to treatment Quality of life Overall survival Pharmacoeconomic analyses For patients included in the early treatment arm, the following criteria will be assessed: • Overall response rate: complete remission (CR) and partial response (PR). • For patients in complete remission the percentage achieving complete molecular remission using the clone specific CDR-III region as follow-up parameter • Duration of response defined as the time elapsed between the first time a response is observed and re-treatment initiation • Adverse events related to treatment (treatment safety) |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Established diagnosis of B-CLL by NCI criteria (Cheson et al., 1996). Diagnosis will be retrospectively confirmed by an expert review committee. Immunophenotyping should be stored in list mode and one stained blood smear available. 2) Binet stage A. 3) First diagnosis within 12 months before inclusion in study. 4) Start of therapy possible within 28 days after completed risk stratification/ randomization. 5) No prior chemotherapy, radiation or antibody treatment. 6) Age > 18 years. 7) Life expectancy > 6 months. 8) ECOG performance status 0 - 2. 9) Written informed consent of patient and treating physician. 10) All parameters for risk stratification present. 11) Willingness to accept contraception if randomized to cohort I for the duration of therapy and 12 months thereafter. 12) Negative serum pregnancy test one week prior to treatment for premenopausal women. 13) Ability to understand the protocol. 14) Possibility of follow up. |
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E.4 | Principal exclusion criteria |
1) Age < 18 years. 2) ECOG performance status > 2. 3) Clinically apparent autoimmune cytopenia, in particular antiglobulin test positive hemolytic anemia (positive antiglobulin test without anemia is not an exclusion criterion) 4) Active secondary malignancy or chemotherapy/radiotherapy for any neoplastic disease other than B-CLL prior to the study 5) Medical condition requiring the prolonged (estimated to be more than one month) use of oral corticosteroids 6) History of anaphylactic reaction following exposure to humanized monoclonal antibodies 7) Patients with active bacterial, viral or fungal infection 8) Known infection with HIV, Hepatitis B or C 9) Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study 10) Pregnancy and/or nursing 11) Concurrent severe diseases which exclude the administration of therapy o heart insufficiency NYHA grade III/IV, LVEF < 50% and or RF <30%, myocardial infarction within the past 6 months prior to study o severe chronic obstructive lung disease with hypoxemia o severe diabetes mellitus o hypertension difficult to control o impaired renal function with creatinine clearance < 70 ml/min according to the formula of Cockroft and Gault o Serum bilirubin > 2 x ULN o Cerebral dysfunction or any other coexisting medical or psychological condition that woud preclude participation in the required study procedures 12) Transformation to aggressive B cell malignancy (i.e. diffuse large cell lymphoma, Richter’s syndrome or prolymphocytic leukemia |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint "event free survival" (EFS) is defined as the time between inclusion in the study until progression, treatment or death. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |