E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rituximab and Campath are two antibodies directed against CD20 and CD52 antigen, respectively. The highest response rate in the B-CLL treatment has been obtained by the association of Fludarabine, Cyclophosphamide and Rituximab. The association of Fludarabine and Campath has also shown high response rate . This study will then compare Campath with Rituximab in association with Fludarabine-Cyclophosphamide.
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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 | 10009310 |
E.1.2 | Term | CLL |
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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 |
progression-free survival (PFS) at 36 month |
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E.2.2 | Secondary objectives of the trial |
* Disease-free survival, event-free survival, overall survival, time to next treatment * ORR (CR and PR) according to NCI, rates of phenotypic and molecular responses * Duration of phenotypic, molecular, NCI CR and PR responses * Response rates and survival times in biological subgroups * Rates of treatment-related adverse effects * Minimal residual disease (MRD) study * Quality of life
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* B-CLL * Age > 18 years * Del 17 p (FISH) negative (< 10 % positives cores) * Binet classification stages B or C * Matutes score 4 or 5, * No previous treatment of CLL by chemotherapy, radiotherapy or immunotherapy, * * except corticosteroids < 1 month * Signed informed consent.
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E.4 | Principal exclusion criteria |
* A BINET stage * Del 17 p (FISH) positive ( > 10 % positives cores) * Age < 18 years * HIV seropositivity * Hepatitis B or C seropositivity (unless clearly due to vaccination) * Performans Status (ECOG) 2 * Life expectancy < 6 months * Clinically significant auto-immune anemia * Active second malignancy currently requiring treatment (except basal cell carcinoma or in situ endometrial carcinoma) and/or less than 5 years CR after breast cancer * Any severe co-morbid conditions such as Class III or IV heart failure, myocardial infarction within months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, severe chronic obstructive pulmonary disease with hypoxemia, uncontrolled diabetes mellitus, or uncontrolled hypertension * CIRS (Cumulative Illness Rating Scale) > 6 (see Appendix for calculation of CIRS score) * Concomitant disease requiring prolonged use of corticosteroids (> 1 month) * Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs * Contraindication to the use of Mabthera® or MabCampath® according to SmPC. * Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia) * Active bacterial, viral or fungal infection * Abnormal renal function with creatinine clearance < 60 ml/min calculated according to the formula of Cockcroft and Gault * Total bilirubin, gamma glutamyltransferase or transaminase levels > 2 ULN. * Any coexisting medical or psychological condition that would preclude participation in the required study procedures * Patient with mental deficiency preventing proper understanding of the requirements of treatment. * Pregnant or breastfeeding women. * Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The objective of this study is to compare, on progression-free survival (PFS) at 36 months, FCR and FCCam in first-line therapy of B and C Binet stage B-CLL patients. |
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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 | No |
E.6.5 | Efficacy | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
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) | 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
| 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 | 71 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Yes |
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 | |
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 |