Chronic Lymphocytic Leukaemia MedDRA version: 17.0 Level: LLT Classification code 10068919 Term: B-cell chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Neoral Soft Gelatin Capsules
Product Name: Neoral Soft Gelatin Capsules
Product Code: Ciclosporin A
Pharmaceutical Form: Capsule, soft
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects of CsA on tumour kinetics in patients with CLL.; Secondary Objective: • 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 ;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;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. ;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. | — |
Countries
United Kingdom
Contacts
Public ContactSonia Fox
University of Birmingham
Outcome results
None listed