Phase I/II clinical trial to assess the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase (PARP) -inhibitor, in relapsed and refractory chronic lymphocytic leukaemia patients with an 11q deletion or ATM mutation and relapsed/refractory patients with T-prolymphocytic leukaemia and mantle cell lymphoma

niversity of Birmingham (UK)0 sites15 target enrollmentFebruary 9, 2010

Overview

Registry

who.int

Start Date

February 9, 2010

End Date

March 1, 2014

Last Updated

4 years ago

Study Type

Interventional

Sex

All

Sponsor

niversity of Birmingham (UK)

•1\. Relapsed or refractory chronic lymphocytic leukaemia (CLL), mantle cell lymphoma or T\-prolymphocytic leukaemia (T\-PLL) patients (World Health Organization \[WHO] Classification of Haematopoietic and Lymphoid Tissues, Fourth Edition) who are not considered to be appropriate for further conventional treatment
•2\. CLL patients only: confirmation of chromosome 11q deletion by fluorescent in situ hybridisation (FISH) or an ATM mutation (ATM mutation requires the presence of both a predicted ATM mutation and demonstration of reduced ATM dependent phosphorylation)\*
•3\. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
•4\. Aged 18 years or older, either sex
•5\. Written informed consent
•6\. Not known to be positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen and hepatitis C antibody
•7\. Estimated life expectancy of greater than 16 weeks
•\*Please note that confirmation of 11q deletion or an ATM mutation prior to registration is not required for CLL patients taking part in phase 1 (dose escalation phase). All other eligibility criteria apply to both phase 1 and phase 2\.

•1\. Receiving treatment for CLL, mantle cell lymphoma or T\-PLL including corticosteroids (greater than 10 mg prednisone/day or equivalent) or have received treatment for CLL, mantle cell lymphoma or T\-PLL for the 4 weeks prior to study entry
•2\. Receiving corticosteroids (at a dose greater than 10 mg prednisone/day or equivalent) for other medical conditions
•3\. Previous treatment with a PARP\-inhibitor, including olaparib
•4\. A known hypersensitivity to olaparib or any excipient of the product
•5\. Treatment with any investigational product within 28 days of registration
•6\. Receiving or have received the following inhibitors of CYP34A:
•6\.1\. Azole antifungals
•6\.2\. Macrolide antibiotics
•6\.3\. Protease inhibitors
•7\. Impaired hepatic or renal function as defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2\.5 x upper limit of normal (ULN), bilirubin greater than 2 x ULN, serum creatinine greater than 2 x ULN