Condition category
Cancer
Date applied
05/08/2015
Date assigned
06/08/2015
Last edited
21/09/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Francesca Yates

ORCID ID

Contact details

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

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 measures

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes