E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pre-treated chronic lymphocytic leukaemia (B-CLL) |
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E.1.1.1 | Medical condition in easily understood language |
Pre-treated chronic lymphocytic leukaemia (B-CLL) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003946 |
E.1.2 | Term | B-Lymphocytic, CLL (Kiel Classification) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary objective of this study is to determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy according to NCI response criteria (also established according to IWCLL guidelines) upon treatment with a combination of bendamustine and alemtuzumab |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are •To determine the safety profile of bendamustine/ alemtuzumab combination therapy in terms of observed toxicities according to NCI CTCAE v3 •To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates •To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment •To determine response rates in all phases by 4-colour flow cytometric MRD analysis •To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status •To define clonal evolution by use of longitudinal FISH cytogenetics •To define T cell subsets including prognostic EM T cells and Treg cells •To document change upon quality of life by use of a standardized QoL questionnaire
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male or female patients with CD23+, CD5+, CD19+ light chain monoclonal B-CLL with treatment indication according to IWCLL criteria (Appendix 4) •1st or greater relapse after fludarabine or any other primary treatment regimen OR Refractory to any previous treatment and simultaneous indication for treatment according to IWCLL criteria (Appendix 4) •Age 18 years and older •ECOG status 0 – 2 •Life expectancy > 6 months •Written informed consent given by the patient •Patient using a reliable means of contraception (e.g. physical barrier, contraceptive pill or patch, spermicide and barrier, or IUD) for the duration of the study. Male patients have to use an adequate contraception method for the duration of study treatment and for 6 months following completion of study treatment. Women of childbearing potential have to use an effective method of contraception for the duration of study participation.
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E.4 | Principal exclusion criteria |
•HIV positive or positive for Hepatitis B or C •Active uncontrolled infection •Hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or to the excipients of any of the applied drugs (e.g. Bendamustine hydrochloride or mannitol) •Previous treatment with bendamustine •Treatment with an experimental drug within the previous 2 months •Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent. •Transformation to aggressive B-cell malignancy (e.g. large B-cell lymphoma, Richter's syndrome, or prolymphocytic leukemia (PLL) •Decreased kidney function with creatinine clearance < 30 ml/min •Patients with severe co-morbidities or major organ dysfunctions (e.g. known severe liver damage, jaundice) •Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina •Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent, or patients unable to comply with requirements of study protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Effucacy - Overall Response Rate |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary objective of this study is to determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy according to NCI response criteria (also established according to IWCLL guidelines) upon treatment with a combination of bendamustine and alemtuzumab. |
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E.5.2 | Secondary end point(s) |
Safety profile of the Bendamustin – Alemtuzumab combination CR rate Achieveable cumulative doses of Bendamustine and Alemtuzumab Response rates in all phases by 4-colour flow cytometric MRD analysis Risk factor analysis (FISH cytogenetics, CD-38/ Zap-70 expression, mutation status) Longitudinal FISH cytogenetics for definition of clonal evolution Longitudinal definition of T-cell subsets (including prognostic EM T-cells and T-reg cells) QoL evaluation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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) | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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End of Trial will be at Last Subject Last Visit at Final Staging 16 month after first study drug administration. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |