a study to assess the effect of ketoconazole on the metabolism of abt-199

Conditions: Non-Hodgkin's Lymphoma

Summary: this is an open-label multicenter, study to assess the pharmacokinetic interaction of ketoconazole with abt-199 in up to 12 subjects with relapsed or refractory non-hodgkin's lymphoma.

this is a phase 1 study designed to assess how the body processes the study drug abt-199 when taken alone and in combination with ketoconazole and to assess the safety of abt-199 in combination with ketoconazole. subjects may enroll in a separate extension study to continue receiving abt-199 after completion of this study.

Eligibility criteria:
inclusion criteria: * subject must have relapsed or refractory non-hodgkin's lymphoma. * subject must have histologically documented diagnosis of non-hodgkin's lymphoma as defined by a b-cell neoplasm in the world health organization (who) classification scheme except as noted in the exclusion criteria. * subject has an eastern cooperative oncology group (ecog) performance score of 0 to 2. * subject must have adequate bone marrow (independent of growth factor support per local laboratory reference range), coagulation, renal and hepatic function: * absolute neutrophil count (anc) greater than or equal to 1000/µl (without growth factor support unless neutropenia is clearly due to underlying disease); * platelets greater than or equal to 75,000/mm3 (unless thrombocytopenia is clearly due to disease-related immune thrombocytopenia or to underlying disease; entry platelet count must be independent of transfusion within 14 days of screening); * hemoglobin greater than or equal to 9.0 g/dl (unless anemia is clearly due to underlying disease; entry hemoglobin must be independent of transfusion within 14 days of screening); * if cytopenias are present, no evidence of myelodysplastic syndrome or hypoplastic bone marrow; * subject must have activated partial thromboplastin time (aptt) and prothrombin time (pt) not to exceed 1.5 × the upper normal limit (uln); * calculated creatinine clearance greater than or equal to 50 ml/min using a 24-hour urine collection for creatinine clearance or per the cockcroft-gault equation; * alanine aminotransferase (alt) and aspartate aminotransferase (ast) less than or equal to 3.0 × uln of institution's normal range; * bilirubin less than or equal to 1.5 × uln. subjects with gilbert's syndrome may have a bilirubin greater than 1.5 × uln per discussion with the abbvie medical monitor. exclusion criteria: * subject has been diagnosed with post-transplant lymphoproliferative disease (ptld), burkitt's lymphoma, burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia (cll), small lymphocytic lymphoma (sll), or mantle cell lymphoma (mcl). * subject is receiving combination anti-retroviral therapy for hiv (due to potential drug-drug interactions between anti-retroviral medications and abt-199, as well as anticipated abt-199 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections). * subject has hypersensitivity to ketoconazole. * subject has a cardiovascular disability status of new york heart association class greater than or equal to 2. class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain. * subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease within the past 6 months that in the opinion of the investigator would adversely affect his/her participating in this study. * subject has malabsorption syndrome or other condition which precludes enteral route of administration (e.g., prior surgical resection). * subject has undergone an allogeneic stem cell transplant.

Keywords: non-hodgkin's lymphoma gdc-0199 safety relapsed refractory abt-199 pharmacokinetics cancer