Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Mrs Kathryn Paterson
ORCID ID
Contact details
Institute for Cancer Studies
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
k.r.paterson@bham.ac.uk
Additional identifiers
EudraCT number
2012-003608-11
ClinicalTrials.gov number
Protocol/serial number
15429
Study information
Scientific title
IciCLLe: Assessment of the Mechanism of Action of Ibrutinib (PCI-32765) in B-cell Receptor Pathway Inhibition in CLL
Acronym
IciCLLe
Study hypothesis
The aim of this feasibility study is to confirm the mechanism of action of Ibrutinib. Results will then inform the design of a randomized phase II/III trial using response as the primary outcome measure to determine whether Ibrutinib shows sufficient evidence of activity in these cohorts of patients.
Ethics approval
14/YH/0034; First MREC approval date 20/02/2014
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
Condition
Topic: Cancer; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)
Intervention
Ibrutinib, B-Cell receptor pathway inhibitor; Follow Up Length: 60 month(s); Study Entry : Registration only
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
Assess the impact on Ibrutinib on: o CLL cell levels as a percentage of total leucocytes in the b; Timepoint(s): Baseline, Day1, Week 1, Week 2, month 1, Month 2, Month 6, month 9, Month 12.
Secondary outcome measures
1. One and two year progression free survival for relapsed/refractory and treatment naïve patients define; Timepoint(s): 1 and 2 years
2. Two and five year overall survival for relapsed/refractory and treatment naïve patients, defined as the; Timepoint(s): 1 and 5 years
3. Best disease response: Complete Remission (CR); Complete Remission with incomplete marrow recovery; Timepoint(s): Week 1, week 2, Month 1, Month 2, Month 6.
4. Biological response (complete, partial or nodal) at 1, 6 and 12 months, assessed according to the; Timepoint(s): 1, 6, 12 months
Overall trial start date
24/04/2014
Overall trial end date
01/04/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Cohort A (Treatment naive)
1. Progressive Stage A, Stage B or Stage C CLL
2. CLL requiring therapy by the IWCLL 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 requiring therapy
2. Refractory CLL defined as any of the following:
3. Failure to achieve a response (CR or PR by IWCLL Criteria) to a purine analogue alone or in combination with chemotherapy, or:
4. Relapse within 6 months of responding to a purine analogue alone or in combination with chemotherapy, or:
5. Relapse within 24 months of responding to a fludarabine, cyclophosphamide and rituximab (FCR), or:
6. Patients with CLL with deletion of chromosome 17p who have failed at least one previous therapy.
7. ECOG performance status (PS) of 0, 1, or 2 (see appendix 6)
8. Life expectancy of at least 6 months
9. Prepared to undergo the stipulated investigations within the trial (including bone marrow examinations)
10. Age = 18
11. Able to give informed consent
Target Gender: Male & Female ; Lower Age Limit 18 years
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). Relapse/refractory
Participant exclusion criteria
Both cohorts A and B
1. Unwilling to undergo the protocol assessments including the bone marrow assessments
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 12 months 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 panocytopenia (nNeutrophils <0.5 x109/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 10 mg or less)
14. Patients requiring or who have received anticoagulation treatment with warfarin or vitamin K antagonists within 1 week of the first dose of ibrutinib
15. Patients requiring concomitant use of strong CYP3A4/5 inhibitors
16. Patients with evidence or history of transformation and/or PLL
Cohort A (Treatment naive)
1. Previous treatment for CLL. This does not include steroids.
Cohort B (Relapsed/Refractory)
1. Previous treatment with ibrutinib or an alternative inhibitor of BCell receptor pathway
Recruitment start date
24/04/2014
Recruitment end date
01/04/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Institute for Cancer Studies
Birmingham
B15 2TT
United Kingdom
Funders
Funder type
Industry
Funder name
Leukaemia and Lymphoma Research (UK); Grant Codes: 12028
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Funder name
Pharmacyclics Inc.
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 provided at time of registration
Basic results (scientific)
Publication list