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
Clinical Trials Information System (CTIS)	2012-003631-36
Protocol serial number	18679
Sponsor	University of Birmingham
Funders	Leukaemia and Lymphoma Research, Gilead Sciences Ltd

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

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-how-idelalisib-works-for-people-with-chronic-lymphocytic-leukaemia-calibre

Contact information

Dr Francesca Yates
Scientific

University of Birmingham
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham, West Midlands
B15 2TT
United Kingdom

Study information

Primary study design	Interventional
Study design	Non-randomised; Interventional; Design type: Treatment
Secondary study design	Non randomised study
Study type	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
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Idelalisib
Primary outcome measure(s)	Proportion of patients achieving MRD-negative remission by IWCLL criteria; Timepoint(s): Ongoing
Key secondary outcome measure(s)	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
Completion date	30/05/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	40
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

United Kingdom
England
Northern Ireland

Study participating centres

St James's University Hospital

Leeds
LS9 7TF
United Kingdom

The Christie NHS Foundation Trust

Manchester
M20 4BX
United Kingdom

Nottingham City Hospital

Nottingham
NG5 1PB
United Kingdom

Queen Elizabeth Hospital

Birmingham
B15 2TH
United Kingdom

Belfast City Hospital

Belfast
BT9 7AB
United Kingdom

The Royal Liverpool University Hospital

Liverpool
L7 8XP
United Kingdom

Kings College Hospital

London
SE5 9RS
United Kingdom

Southampton General Hospital

Southampton
SO16 6YD
United Kingdom

Churchill Hospital

Oxford
OX3 7LJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
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
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN52057158_BasicResults_20Sep22.pdf: Basic results

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.