This is an Open-label Study Designed to Determine the Safety, Pharmacokinetics, Maximum Tolerated Dose, and the Recommended Phase 2 Dose of ABT-199 When Administered in Relapsed or Refractory Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Their Standard Therapy.
- Greater than or equal to 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1
- Diagnosis of multiple myeloma previously treated with at least 1 prior line of
therapy (dose escalation only) or less than 4 separate lines of therapy (Safety
Expansion only) including a proteasome inhibitor and an IMiD(r) or immunomodulatory
agent (e.g., thalidomide, lenalidomide). Induction therapy and following autologous
stem cell transplant are considered a single line of therapy.
- Measurable disease at Screening: Serum monoclonal protein greater than or equal to 1
g by protein electrophoresis or greater than or equal to 200 mg monoclonal protein in
the urine on 24-hr electrophoresis or serum immunoglobulin free light chain greater
than or equal to 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free
light chain ratio.
- Subject has a history of autologous stem cell transplant, must be greater than 100
days post-transplant prior to first dose of study drug and have adequate bone marrow
independent of any growth factor support, and have recovered from any transplant
- Subject must have adequate coagulation, renal, and hepatic function, per laboratory
reference range at Screening.
- Exhibits evidence of other clinically significant uncontrolled condition(s),
including, but not limited to: uncontrolled systemic infection (viral, bacterial, or
fungal), diagnosis of fever and neutropenia within 1 week prior to first dose of
- Cardiovascular disability status of New York Heart Association Class greater than 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.
- Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic,
immunologic, cardiovascular, pulmonary or hepatic disease, that in the opinion of the
investigator, would adversely affect his/her participation in the study.
- History of other active malignancies other than multiple myeloma within the past 3
years prior to study entry, with the following exceptions: adequately treated in situ
carcinoma of the cervix uteri, basal cell carcinoma of the skin or localized squamous
cell carcinoma of the skin, previous malignancy confined and surgically resected (or
treated with other modalities) with curative intent.
- Tested positive for HIV or hepatitis.