A Study to Assess the Effect of Ketoconazole on the Metabolism of ABT-199

• Status: Completed
• Trial end date: 2014-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AbbVie
• Collaborator: Genentech, Inc.
• Treatments: Ketoconazole; Venetoclax

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.