Chronic lymphocytic leukaemia MedDRA version: 21.1 Level: LLT Classification code 10068852 Term: B-cell chronic lymphocytic leukaemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Zydelig
Product Name: Zydelig
Pharmaceutical Form: Tablet
INN or Proposed INN: Idelalisib formerly CAL-101, GS-1101
CAS Numb
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Chronic lymphocytic leukaemia requiring therapy 2. Relapsed/refractory CLL defined as any of the following: - Failure to achieve a response (CR or PR) to, or progression during or after, ibrutinib (or an alternative Btk inhibitor) Or: - Patients who are unable to tolerate ibrutinib (or an alternative BTK inhibitor) or in whom it is contraindicated. _And_ where at least one of the following criteria apply • Patients with CLL with deletion of chromosome 17p who have failed at least one previous therapy • Failure to achieve a response (CR or PR by IWCLL criteria) to a purine analogue alone or in combination with chemotherapy, or: • Relapse within 6 months of responding to a purine analogue alone or in combination with chemotherapy, or: • Relapse at any time after fludarabine, cyclophosphamide and rituximab (FCR) or chemotherapy plus rituximab (or an alternative anti-CD20 antibody): 3. ECOG performance status (PS) of 0, 1, or 2 (see Appendix 5). 4. Life expectancy of at least 6 months 5. Prepared to undergo the stipulated investigations within the trial (including bone marrow examinations) 6. Age =18 7. Able to give informed consent Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Previously untreated for CLL 2. Unwilling to undergo the protocol assessments including the bone marrow assessments 3. Active infection at the time of registration, history of chronic or recurrent infection 4. Other severe, concurrent (particularly cardiac or pulmonary) diseases or mental disorders that could interfere with their ability to participate in the study 5. Use of prior investigational agents within 6 weeks 6. Pregnancy or lactation 7. Unwilling to use appropriate contraception during and for 30 days following treatment 8. CNS involvement with CLL 9. Mantle cell lymphoma 10. Known HIV positive 11. Active or prior Hepatitis B or C 12. Active secondary malignancy excluding basal cell carcinoma 13. Persisting severe pancytopenia (neutrophils <0.5 x109/L) or transfusion dependent anaemia unless due to direct marrow infiltration by CLL. This is to be confirmed via bone marrow biopsy. 14. Active haemolysis (not controlled with prednisolone at 20mg or less) 15. Hypersensitivity to idelalisib or to any of the excipients listed in the Summary of Product Characteristics (SmPC) 16. Previous treatment with idelalisib or another PI3K inhibitor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the mechanism of action of idelalisib ; Secondary Objective: To assess the biological response to idelalisib To assess 1 and 2 year progression free survival To assess the 1 and 5 year overall and disease free survival of patients ;Primary end point(s): •Proportion of patients achieving MRD-negative remission by IWCLL criteria (depletion of CLL below 0.01% in the peripheral blood and bone marrow);Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • CLL cell levels as a percentage of total leucocytes in the bone marrow (BM) and absolute counts in the peripheral blood (PB). • The proportion of patients with >5%, 0.5-5%, <0.5% CLL cells in cell cycle (expressing Ki67) in the peripheral blood and bone marrow after 6-9 months of idelalisib. • Change in the expression levels of CD10, CD103, CD11c, CD195, CD196, CD20, CD200, CD22, CD23, CD25, CD27, CD305, CD31, CD38, CD39, CD43, CD49d, CD5, CD79b, CD81, CD95, IgD, IgG, or IgM on CLL cells relative to baseline by more than 50% and at least 500 arbitrary units in median fluorescence intensity. • Best disease response: Complete Remission (CR); Complete Remission with incomplete marrow recovery (Cri) or Partial Remission (PR), to treatment within the first 6 months of treatment assessed according to the IWCLL Response Criteria (revised 2008) • 1 and 2 year progression free survival for relapsed/refractory and treatment naïve patients defined as time from date of registration to date of progression (per the 2008 IWCLL criteria) or death from any cause. • 1 and 5 year overall survival for relapsed/refractory and treatment naïve patients, defined as the time from date of registration to the date of death from any cause. •Toxicity of idelalisib within 6 months. ;Timepoint(s) of evaluation of this end point: Up to 5 years | — |
Countries
United Kingdom
Contacts
Public ContactFrancesca Yates
Cancer Research UK Clinical Trials Unit
Outcome results
None listed