Chronic Lymphocytic leukaemia MedDRA version: 14.1 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864
Conditions
Interventions
Product Name: Ibrutinib
Product Code: PCI-32765
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort A (Treatment naive) • Progressive Stage A, Stage B or Stage C CLL • CLL requiring therapy by the IWCLL criteria • ECOG performance status (PS) of 0, 1, or 2 • Life expectancy of at least 6 months • Age =16 • Age =65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: Both cohorts A and B • Unwilling to undergo the protocol assessments including the bone marrow assessments • Active infection • Other severe, concurrent (particularly cardiac or pulmonary) diseases or mental disorders that could interfere with their ability to participate in the study • Use of prior investigational agents within 6 weeks • Pregnancy or lactation • Unwilling to use appropriate contraception during and for 12 months following treatment • CNS involvement with CLL • Mantle cell lymphoma • Known HIV positive • Active or prior Hepatitis B or C • Active secondary malignancy excluding basal cell carcinoma • 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) • Active haemolysis (not controlled with Prednisolone at 10 mg or less) • Patients requiring or who have received anticoagulation treatment with warfarin or vitamin K antagonists within 1 week of the first dose of ibrutinib • Patients requiring concomitant use of strong CYP3A4/5 inhibitors • Patients with evidence or history of transformation and/or PLL Cohort A (Treatment naive) • Previous treatment for CLL. This does not include steroids. Cohort B (Relapsed/Refractory) • Previous treatment with ibrutinib or an alternative inhibitor of B-Cell receptor pathway
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this clinical study is to investigate how the drug, called ibrutinib (previously PCI32765), affects the rate of growth, and the lifespan, of leukaemia cells in patients with Chronic Lymphocytic Leukaemia (CLL). The purpose of the trial is to gain a better understanding of how the drug works in order to use it in logical combinations with other drugs that treat CLL which will be tested in future clinical studies. We hope to achieve this by taking frequent blood samples from patient being treated with the drug and analysing them using methods called flow-cytometery and histology. ;Secondary Objective: The amount of patients should a Complete Remission (CR) Complete Remission with incomplete marrow recovery (Cri) or Partial Remission (PR), to ibrutinib at 6 months, assessed according to the IWCLL Response Criteria The changes in CLL cell protein expression levels. At 6 and 12 months we will also be looking at where and how the drug is acting within the body by measuring the biological response in both the circulating CLL cells blood and in the CLL cells in the bone marrow. We will also study the CLL cells that are responsible for increasing the number of cancer cells. To determine the amount of patients for who their disease has not worsened at 1 and 2 years. To determine the amount of patients alive 1 and 5 years after the start of treatment. To assess the toxicity of the drug over 6 months of treatment. ;Primary end point(s): • Assessment of the proliferating cells in the peripheral blood and bone marrow by flow cytometry and histology ;Timepoint(s) of evaluation of this end point: Baseline, day 1, day 2, week 1, Week 2, 1 month, 2 month, 6 month, 9 months and 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Disease response, whether complete, CRi or partial, to ibrutinib at 6 months, according to the 2008 IWCLL Criteria • Changes in CLL cell levels and proliferating compartment • Biological response (complete, partial or nodal) at 6 and 12 months, according to the modified IWCLL Criteria. • 1 and 2 year progression free survival for relapsed/refractory and treatment naïve patients • 1 and 5 year overall survival for relapsed/refractory and treatment naïve patients • Toxicity of ibrutinib within 6 months ;Timepoint(s) of evaluation of this end point: • Disease response IWCLL, at 6 months • Changes in CLL cell levels and proliferating compartment at 6 and 12 months • Biological response, modified IWCLL Criteria, at 6 and 12 months • Progression free survival at 1 and 2 years • Overall survival at 1 and 5 years • Toxicity of ibrutinib within 6 months | — |
Countries
United Kingdom
Contacts
Public ContactKathryn Paterson
University of Birmingham
Outcome results
None listed