Trial of Idelalisib in Patients With Relapsed Diffuse Large B-cell Lymphoma

Inclusion criteria

• Age >18 years.
• Histologically confirmed diffuse large B-cell lymphoma (DLBCL) , including transformed low grade lymphoma, with either:

• Refractory disease: defined as disease progression while receiving their most recent prior cytotoxic chemotherapy (single-agent immunotherapy as maintenance is not considered cytotoxic therapy).
• Persistent disease: defined as stable disease or partial response at the completion of their most recent prior cytotoxic chemotherapy.
• Relapsed/recurrent disease: defined as complete response at the end of their most recent prior cytotoxic chemotherapy with subsequent relapse or disease recurrence.
• Subjects must have received prior rituximab and may have received up to 5 prior regimens containing cytotoxic chemotherapies.
• Subjects must not be candidates for high-dose chemotherapy with autologous stem cell support (ASCT), due to one or more of the following factors: relapse after high dose chemotherapy, age, comorbid disease, performance status, or persisting toxicities from prior chemotherapy.
• Absolute neutrophil count (ANC) >1.0 x 109/L, unless related to bone marrow infiltration.
• At least 1 measurable disease lesion that is >1.0 cm in 2 perpendicular dimensions, with the product diameter >2.25 cm2 by computed tomography (CT) or magnetic resonance imaging (MRI).
• Negative serum pregnancy test within 1 week before first treatment if the subject is a woman of childbearing potential. The use of highly-effective contraception methods* are required during the study for women of child-bearing potential. Due to the toxicity of idelalisib, women who will use a hormonal contraceptive must in addition also use a barrier method, since it is currently unknown whether idelalisib may reduce the effectiveness of hormonal contraceptives. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant.
• WHO performance status 0 - 3.
• Written informed consent.

Exclusion criteria

• Prior allogeneic hematopoietic stem cell transplant (HSCT).
• Prior treatment with PI3K inhibitors.
• Serum total bilirubin ≥ 1.5 x ULN (unless elevated due to Gilbert's syndrome).
• Serum ALT and AST ˃ 2.5 x ULN.
• Estimated Creatinine Clearance < 10 ml/min.
• Known seropositivity for human immunodeficiency virus (HIV).
• Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
• Known history of drug induced pneumonitis.
• On-going inflammatory bowel disease.
• Evidence of serious active infection (eg, requiring an intravenous [IV] antibiotic, antiviral, or antifungal agent), or subjects with a recent history of deep tissue infections such as fascitis or osteomyelitis.
• Chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational drugs/devices <10 days before first dose of investigational product in this study. Subjects receiving high doses of corticosteroids must have been tapered to a stable dose at least 7 days before the first dose of investigational product.
• Pregnant or breastfeeding women.
• Symptomatic central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected.
• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition).
• Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for >2 years.
• Previous myocardial infarction or pulmonary hypertension <6 months before first dose of investigational product.
• History of clinically significant ventricular arrhythmia, prolonged QTc interval or unexplained syncope.
• Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.