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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic leukaemia |
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 principal research objective is to compare consolidation therapy with alemtuzumab against no consolidation therapy with respect to progression free survival. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: •To assess the eradication of detectable minimal residual disease (MRD) following consolidation therapy with alemtuzumab •To evaluate overall response rate defined as complete or partial remission by IWCLL criteria •To compare consolidation therapy with alemtuzumab against no consolidation therapy with respect to overall survival •To compare time to next treatment for alemtuzumab consolidation against no consolidation •To evaluate and compare duration of MRD negativity, progression free survival and overall survival in patients who are and who become MRD negative •To explore MRD growth rate following MRD relapse with respect to progression free survival and overall survival •To assess the safety and toxicity of alemtuzumab •To assess quality of life using the EORTC QLQ-C30 and CLL Specific Module EORTC QLQ-CLL16 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
UK CLL Trials BioBank The UK CLL Trials BioBank aims to identify biomarkers that predict therapeutic response to the treatments being evaluated. Participants entering the study are therefore requested to donate bone marrow, blood and saliva samples prior to the commencement of therapy. Additional samples are requested at specific time points thereafter. These samples will be used for a range of studies of direct relevance to the treatment of CLL. |
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E.3 | Principal inclusion criteria |
• At least 18 years old • Previous confirmation of B-CLL with a characteristic immunophenotype (for example, CD5+, CD19+, CD23+ lymphoproliferative disorder) on peripheral blood flow cytometry • Peripheral B-Cell count <5x109l • Maximum of three prior therapies received for CLL treatment • First MRD positive peripheral blood sample between 6 and 12 months since completing most recent therapy for CLL • Response to most recent chemotherapy treatment for CLL with PR, CRi or CR • Absence of clinically or radiologically evident lymphadenopathy (largest lymph node <2cm in minimum diameter) • Creatinine and bilirubin <2 times upper limit of normal unless secondary to direct infiltration of the liver by CLL or haemolysis • World Health Organisation (WHO) performance status (PS) of 0 or 1 • Able to provide written informed consent
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E.4 | Principal exclusion criteria |
Patients with the following characteristics are ineligible for this trial:
• Disease progression after response to latest therapy • Active infection • Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies • Previous treatment with alemtuzumab • Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 6 months after treatment has finished • Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception whilst receiving treatment and for 6 months after treatment has finished, unless they are surgically sterile • CNS involvement with CLL • Mantle cell lymphoma • Other severe, concurrent diseases or mental disorders • HIV positive • Patient has active or prior Hepatitis B or C • Active secondary malignancy excluding basal cell carcinoma • Persisting severe pancytopenia (neutrophils <0.5 x 109/l or platelets <50 x 109/l) or transfusion dependent anaemia • Active haemolysis • Patients previously treated with allogeneic SCT
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is progression free survival (PFS). This is defined as time from randomisation to first documented evidence of disease progression 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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
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 | 25 |
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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The end of trial is defined as the date of the collection of the last participant's last data item. Long term follow up will continue via the CLL long-term follow up database. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 29 |