Additional identifiers
EudraCT number
2012-003631-36
ClinicalTrials.gov number
Protocol/serial number
18679
Study information
Scientific title
Assessment of the Mechanism of Action of idelalisib (CAL101) in B-cell Receptor Pathway Inhibition in CLL: a non-randomised interventional trial
Acronym
CALiBRe
Study hypothesis
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
NRES Committee Yorkshire & The Humber - Leeds West, 11/02/2015, ref: 15/YH/0020
Study design
Non-randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
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 names
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 trial start date
27/03/2012
Overall trial end date
30/05/2017
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
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
Participant 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
Recruitment start date
13/07/2015
Recruitment end date
31/12/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St James's University Hospital
Leeds
LS9 7TF
United Kingdom
Trial participating centre
The Christie NHS Foundation Trust
Manchester
M20 4BX
United Kingdom
Trial participating centre
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Belfast City Hospital
Belfast
BT9 7AB
United Kingdom
Trial participating centre
The Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom
Trial participating centre
Kings College Hospital
London
SE5 9RS
United Kingdom
Trial participating centre
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Trial participating centre
Churchill Hospital
Oxford
OX3 7LJ
United Kingdom
Sponsor information
Organisation
University of Birmingham
Sponsor details
Edgbaston
Birmingham
West Midlands
B15 2TT
United Kingdom
Sponsor type
University/education
Website
http://www.birmingham.ac.uk/research/activity/mds/trials/crctu/index.aspx
Funders
Funder type
Charity
Funder name
Leukaemia and Lymphoma Research
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Gilead Sciences Ltd
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)
Publication list