E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated mail or female patients with newly diagnosed binet stage A CLL, as defined by NCI criteria. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
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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 |
A comparison of the effect on event free survival of deferred versus immediate treatment with FCR in Binet stage A patients at high risk of disease progression.
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 |
For all patients: progression free survival, 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 tested: overall response rate: complete remission and partial response, for patients in complete remission the percentage achievingcomplete molecular remission using the clone specific CDR-III region as follow-up parameter, duration of response, adverse events related to treatment/safety of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Established dg of B-CLL by NCI criteria. 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. All parameters for risk stratification present. 10. Willingness to accept contraception if randomiyed to Cohort I for the duration of therapy and 12 months thereafter. 11. Negative serum pregnancy test one week prior to trešatmentř for premenopausal women. 12. Possibility of follow-up.
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E.4 | Principal exclusion criteria |
1. Age < 18 years. 2. ECOG performance status > 2. Clinically apparent autoimmune cytopenia, in particular antiglobulin test positive hemolytic anaemia. 4. Active secondary malignancy or chemotherapy/radiotherapy for any neoplastic disease other than B-CLL prior to the study. 5. Medical condition requiring 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. Pregnancy and/or nursing. 10. Concurrent severe disease which exclude the administratio of therapy: - heart insufficiency NYHA grade III/IV; LEVF < 50% and or RF < 30%, MI within the past6 months prior this study -severe chronic obstructive lung disease with hypoxemia -severe DM - hypertension difficult to control -impaired renal function with creatinine clearence < 70ml/min according to the formula Cockroft-Gault -serum bilirubin > 2x ULN -cerebral dysfunction or any other coexisting medical or psychological condition that would preclude participation in the required study procedures 11. Transformation to aggresive 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) |
Event free survival, defined aby time elapsed from randomization to progression, treatment or death (EFS) |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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 | 2 |
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 | 2 |