A Phase I Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Multiple Myeloma
Rochester, Minn., Phoenix/Scottsdale, Ariz.
Trial status: Open for Enrollment
Why is this study being done?
The primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and recommended phase 2 dose (RPTD) of ABT-199 when administered in subjects with relapsed or refractory multiple myeloma.
Who is eligible to participate?
- ECOG (Eastern Cooperative Oncology Group) performance score of 1 or 0.
- Diagnosis of multiple myeloma previously treated with more than 1 prior line of therapy, induction therapy followed by stem cell transplant and maintenance therapy will be considered a single line of therapy (dose escalation only); or fewer than 4 separate lines of therapy (safety expansion only) including a proteasome inhibitor and an IMiD or immunomodulatory agent (e.g., thalidomide, lenalidomide), induction therapy followed by stem cell transplant and maintenance therapy will be considered a single line of therapy.
- Measurable disease at Screening: Serum monoclonal protein of at least 1.0 g/dL by protein electrophoresis or at least 200 mg of monoclonal protein in the urine on 24-hr electrophoresis or serum immunoglobulin free light chain of at least 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.
- Subjects with a history of autologous or allogenic stem cell transplantation must have adequate peripheral blood counts independent of any growth factor support, and have recovered from any transplant related toxicity(s) and be at least 100 days post-autologous transplant prior to first dose of study drug or at least 6 months post-allogenic transplant prior to first dose of study drug and not have active graft-versus-host disease (GVHD), i.e., requiring treatment.
- Meet the following laboratory parameters, per the reference range: ANC of at least 1000/μL (Subjects with bone marrow that is heavily infiltrated with underlying disease may use growth factor support to achieve ANC eligibility criteria, discussion should occur between investigator and sponsor medical monitor regarding any subject's use of growth factor to meet ANC criteria), AST and ALT not higher than 3 x ULN, Calculated creatinine clearance of at least 30 mL/min using a modified Cockcroft-Gault calculation (using Ideal Body Weight instead of Mass, subjects with calculated creatinine clearance less than or equal to 50 mL/min should have medical management discussed with sponsor medical monitor), platelet count of at least 30,000 mm³ (independent of transfusion for 2 weeks), hemoglobin of at least 9.0 g/dL, total bilirubin not higher than 1.5 x ULN (subjects with Gilbert's Syndrome may have bilirubin higher 1.5 x ULN with approval of sponsor medical monitor) and aPTT and PT not higher than 1.2 x ULN.
- 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 study drug.
- 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 or hepatic disease, within the last 6 months that, in the opinion of the investigator, would adversely affect his/her participation in the study. For subjects who have required an intervention for any of the above diseases within the past 6 months, a discussion with the investigator and the AbbVie medical monitor must occur.
- 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.
- Seropositive for hepatitis A, hepatitis B surface antigen, or hepatitis C virus antibody or RNA. Subjects with serologic evidence of prior vaccination to HBV may participate.