Non-Hodgkin's Lymphoma
Conditions
Keywords
non-Hodgkin's lymphoma, GDC-0199, Safety, Relapsed, Refractory, ABT-199, Pharmacokinetics, Cancer
Brief 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.
Detailed description
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.
Interventions
DRUGABT-199
Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole
DRUGKetoconazole
Subjects will be dosed with ABT-199, then dosed with ABT-199 in combination with ketoconazole
Sponsors
Genentech, Inc.
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of maximum observed plasma concentration (Cmax), time to Cmax (peak time, Tmax), terminal phase elimination rate constant (beta), terminal phase elimination half-life (t1/2), & area under the plasma concentration-time curve (AUC) of ABT-199 | Measured pre-dose and up to 96 hours post-dose ABT-199 | Blood samples for pharmacokinetic (PK) analysis of ABT-199 will be collected at designated timepoints to assess the PK parameters for ABT-199 alone relative to ABT-199 with ketoconazole |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events | Measured up to 30 days after the last dose of study drug | Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study |
| Percentage of subjects with adverse events | Measured up to 30 days after the last dose of study drug | Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study |
| Change in physical exam finding, including vital signs | Measured from Day 1 up to 30 days after the last dose of study drug | Body temperature, weight, blood pressure, heart rate |
| Change in clinical laboratory test results | Measured from Day 1 up to 30 days after the last dose of study drug | Chemistry, coagulation, hematology, urinalysis |
| Change in cardiac assessment findings | Measured from Day 1 up to Day 12 | Electrocardiogram |
Countries
United States
Outcome results
None listed