E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukaemia |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068919 |
E.1.2 | Term | B-cell chronic lymphocytic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To investigate the effects of CsA on tumour kinetics in patients with CLL. |
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E.2.2 | Secondary objectives of the trial |
• Toxicity of CsA in patients with CLL (toxicities will be measured and graded according to CTCAE criteria v4). • Spontaneous intra-patient variation in the proliferation (growth), release and loss of CLL cells from the circulation. • Time to the maximum release of labelled CLL cells into the circulation with CsA therapy. • Rate of loss of labelled CLL cells from the circulation with CsA therapy • Complete response rate* - Complete Remission after 8 weeks and 6 months CsA • Overall response rate* (Complete Remission + Partial Remission) after 8 weeks and 6 months of CsA
Translational outcome measures: • Stability of unsorted CLL cells for 2H-Glu proliferation assays to assess the feasibility of future multi-site studies, i.e. do the samples need to be sorted at site and frozen or could they be sorted centrally with 24 hours without loss of quality.
If funding allows, the following translational outcome will be assessed: Effect of CsA on: Phenotype and activation sta |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Stage A or B CLL (Binet system) not requiring therapy by conventional criteria • ≤ 2 lines of previous therapy for CLL • Age ≥18 • ECOG performance status ≤2 • Life expectancy >12 months • No therapy for CLL in previous 3 months (including glucocorticoids) • CD38+ve; ≥ 7% • Normal renal function (eGFR >60mls/min) • Normal liver function (AST and / or ALT <1.5 ULN) • Negative serology for Hepatitis B, C and HIV • Valid informed consent |
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E.4 | Principal exclusion criteria |
• Active infection • Active autoimmune disease (requiring therapy) • Diabetes Mellitus • Previous myocardial infarction or history of cardiac dysrhythmia. • Uncontrolled hypertension • Taking medication known to cause serious interaction with CsA where the interaction cannot be prevented by monitoring and adjusting CsA level • Fludarabine refractory disease (Non response to or relapse within 6 months of fludarabine containing regimen) • Previous bone marrow transplant • History of prior malignancy, with the exception of certain skin cancers and malignancies treated with curative intent and with no evidence of active disease for more than 3 years. • Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) • Patients and partners of childbearing potential not willing to use effective contraception during and for 3 months after therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in proliferation rate of CLL cells from day 0 of cycle 2 to day 56 (after 4 weeks of CsA therapy) will measured by deuterated glucose incorporation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary outcome will be evaluated after all patients have received treatment with Cyclosporin A for 4 weeks. |
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E.5.2 | Secondary end point(s) |
Secondary outcome measures: • Toxicity of CsA in patients with CLL (toxicities will be measured and graded according to CTCAE criteria v4). • Spontaneous intra-patient variation in the proliferation, release (optional) and loss of CLL cells from the circulation. • Effect of CsA on the release of labelled CLL cells into the circulation (optional). • Effect of CsA on the loss of labelled CLL cells from the circulation • Complete response rate* - Complete Remission after 8 weeks and 6 months CsA • Overall response rate* (Complete Remission + Partial Remission) after 8 weeks and 6 months of CsA *Response as defined by the guidelines from the International Workshop on Chronic Lymphocytic Leukemia. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary outcome will be analysed 2 months after the last patient has completed Cyclosporin A therapy. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | 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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LVLS plus 6 months for final data cleaning |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |