A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 319 in Adult Subjects With Relapsed or Refractory Lymphoid Malignancies

Fecha de inicio: 1 de abril de 2011

Inclusion Criteria: \- Part 1 (Dose Exploration): Relapsed or refractory lymphoid malignancy of the following type for which standard treatment does not exist or is no longer effective: B-cell Chronic Lymphocytic Leukemia (CLL) confirmed by immunophenotype or Non-Hodgkin Lymphoma: Low or intermediate grade B-cell NHL, mantle cell lymphoma, non-cutaneous T-cell NHL confirmed by histology and/or immunophenotype * Part 2 (Dose Expansion): Subjects must have relapsed or refractory B-cell Chronic Lymphocytic Leukemia confirmed by immunophenotype for which standard treatment does not exist or is no longer effective. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 * Life expectancy of \> 3 months, in the opinion of the investigator * Men or women ≥ 18 years old * Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (unless due to disease-related bone marrow involvement as documented by bone marrow biopsy, ≥ 0.5 x 109/L) Platelet count ≥ 50 x 109/L (without a transfusion within 14 days before enrollment) Hemoglobin ≥ 9 g/dL \- Hepatic function, as follows: Aspartate aminotransferase (AST) \< 3.0 x ULN Alanine aminotransferase (ALT) \< 3.0 x ULN Alkaline phosphatase (ALP) \< 2.0 x ULN (\< 5 x ULN in subjects whom the PI and sponsor agree that clinical data suggest an extrahepatic source of elevation) Total bilirubin \< 1.5 x ULN (\< 3.0 x ULN for subjects with documented Gilbert's Disease or for whom the indirect bilirubin level suggests an extrahepatic source of elevation) Amylase ≤ 2.0 x IULN Lipase ≤ 2.0 x IULN Exclusion Criteria: * Primary or disseminated tumor involving the central nervous system (CNS) * A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years * History of allogeneic stem-cell (or other organ) transplantation * Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome * QTcF interval \> 470 msec * Active or chronic hepatitis B or hepatitis C infection, determined by serologic tests * Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment