CALiBRe: Assessment of the Mechanism of Action of idelalisib (CAL101) in B-cell Receptor Pathway Inhibition in CLL
| ISRCTN | ISRCTN52057158 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52057158 |
| EudraCT/CTIS number | 2012-003631-36 |
| Secondary identifying numbers | 18679 |
- Submission date
- 05/08/2015
- Registration date
- 06/08/2015
- Last edited
- 07/12/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr Francesca Yates
Scientific
Scientific
University of Birmingham
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham, West Midlands
B15 2TT
United Kingdom
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Assessment of the Mechanism of Action of idelalisib (CAL101) in B-cell Receptor Pathway Inhibition in CLL: a non-randomised interventional trial |
| Study acronym | CALiBRe |
| Study objectives | The aims of this mechanistic study are to confirm: 1. The mechanism of action of idelalisib 2. The biological response to idelalisib in two cohorts of patients: 2.1. Treatment naïve 2.2. Relapsed/refractory CLL |
| Ethics approval(s) | NRES Committee Yorkshire & The Humber - Leeds West, 11/02/2015, ref: 15/YH/0020 |
| Health condition(s) or problem(s) studied | Topic: Cancer; Subtopic: Haematological Oncology; Disease: Leukaemia(Chronic Lymphocytic Leukaemia) |
| Intervention | All patients will receive the same treatment (idelalisib) which is taken orally twice daily. Study Entry : Registration only |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Idelalisib |
| Primary outcome measure | Proportion of patients achieving MRD-negative remission by IWCLL criteria; Timepoint(s): Ongoing |
| Secondary outcome measures | 1. CLL cell levels as a percentage of total leucocytes in the bone marrow (BM) and absolute counts in the peripheral blood (PB) 2. 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 3. 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 4. 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 5. Biological response at 1, 6 and 12 months, assessed according to the Modified IWCLL Response Criteria 6. 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 7. 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 8. Toxicity of idelalisib within 6 months |
| Overall study start date | 27/03/2012 |
| Completion date | 30/05/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 40; UK Sample Size: 40; Description: 2 cohorts of 20 patients each: cohort A) treatment naive; cohort B) relapsed/refractory |
| Total final enrolment | 23 |
| Key inclusion criteria | Cohort A (treatment naïve) 1. Progressive stage A, stage B or stage C CLL 2. CLL requiring therapy by the IWCLL Response criteria 3. ECOG performance status (PS) of 0,1 or 2 4. Life expectancy of at least 6 months 5. Age ≥18 6. Prepared to undergo the stipulated investigations within the trial (including bone marrow examinations) 7. Able to give informed consent Cohort B (relapsed/refractory) 1. CLL patients requiring therapy 2. Refractory CLL defined as any of the following: 2.1. Failure to achieve a response (CR or PR by IWCLL criteria) to a purine analogue alone or in combination with chemotherapy, or: 2.2. Relapse within 6 months of responding to a purine analogue alone or in combination with chemotherapy, or: 2.3. Relapse at any time after fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine plus rituximab or: 2.4. Patients with CLL with deletion of chromosome 17p who have failed at least one previous therapy. 3. ECOG performance status (PS) of 0, 1 or 2 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 |
| Key exclusion criteria | Both cohorts A and B 1. Unwilling to undergo the protocol assessments including the bone marrow examinations 2. Active infection 3. Other severe, concurrent (particularly cardiac or pulmonary) diseases or mental disorders that could interfere with their ability to participate in the study 4. Use of prior investigational agents within 6 weeks 5. Pregnancy or lactation 6. Unwilling to use appropriate contraception during and for 30 days following treatment 7. CNS involvement with CLL 8. Mantle cell lymphoma 9. Known HIV positive 10. Active or prior hepatitis B or C 11. Active secondary malignancy excluding basal cell carcinoma 12. Persisting severe pancytopenia (neutrophils <0.5 x 109/L) or transfusion dependent anaemia unless due to direct marrow infiltration by CLL (to be confirmed via bone marrow biopsy) 13. Active haemolysis (not controlled with prednisolone at 20 mg or less) 14. Hypersensitivity to the active substance or to any of the excipients listed in the SmPC Cohort A (treatment naive) Previous treatment for CLL. This does not include steroids Cohort B (relapsed/refractory) Previous treatment with idelalisib or an alternative inhibitor of Bcell receptor pathway |
| Date of first enrolment | 13/07/2015 |
| Date of final enrolment | 31/12/2016 |
Locations
Countries of recruitment
- England
- Northern Ireland
- United Kingdom
Study participating centres
St James's University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
The Christie NHS Foundation Trust
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom
NG5 1PB
United Kingdom
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Belfast City Hospital
Belfast
BT9 7AB
United Kingdom
BT9 7AB
United Kingdom
The Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom
L7 8XP
United Kingdom
Kings College Hospital
London
SE5 9RS
United Kingdom
SE5 9RS
United Kingdom
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
SO16 6YD
United Kingdom
Churchill Hospital
Oxford
OX3 7LJ
United Kingdom
OX3 7LJ
United Kingdom
Sponsor information
University of Birmingham
University/education
University/education
Edgbaston
Birmingham, West Midlands
B15 2TT
England
United Kingdom
| Website | http://www.birmingham.ac.uk/research/activity/mds/trials/crctu/index.aspx |
|---|---|
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Charity
Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Gilead Sciences Ltd
No information available
Results and Publications
| Intention to publish date | 30/09/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 20/09/2022 | 30/09/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
07/12/2022: The intention to publish date and IPD sharing statement were added.
30/09/2022: The basic results of this trial have been uploaded as an additional file. Total final enrolment added.
