Study Evaluating ABT-199 in Subjects With Relapsed or Refractory Multiple Myeloma
The phase 1 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 (venetoclax) when administered in subjects with relapsed or refractory multiple myeloma. This study will also assess the safety profile and PK of venetoclax in combination with dexamethasone in subjects with t(11;14)-positive multiple myeloma. The phase 2 primary objective is to further evaluate the objective response rate (ORR) and very good partial response or better rate (VGPR+) in subjects with t(11;14)-positive multiple myeloma.
- Relapsed/Refractory Multiple Myeloma
- Eligible Ages
- Between 18 Years and 99 Years
- Eligible Genders
- Accepts Healthy Volunteers
- ECOG (Eastern Cooperative Oncology Group) performance score of 1 or 0. Subjects in the Phase 2 portion: ECOG performance score of 2, 1, or 0.
- Diagnosis of multiple myeloma previously treated with at least one prior line of therapy. Induction therapy followed by stem cell transplant and maintenance therapy will be considered a single line of therapy. For Safety Expansion, subjects must have been previously treated with a proteasome inhibitor (e.g., bortezomib) and an immunomodulatory agent (e.g., thalidomide, lenalidomide). For Venetoclax-Dexamethasone Combination, subjects must have been been previously treated with a proteasome inhibitor (e.g., bortezomib) and an immunomodulatory agent (e.g., thalidomide, lenalidomide) AND have t(11;14)-positive multiple myeloma per the central lab testing. For Phase 2, subjects must have MM positive for the t(11;14) translocation, as determined by an analytically validated fluorescence in situ hybridization (FISH) assay per the central laboratory testing (enrollment with local t(11;14)-positive FISH results only will be considered at the discretion of the TA MD) Subjects must have evidence of disease progression on or within 60 days of last dose of most recent previous treatment based on IMWG criteria AND Subject must have previously received at least 2 lines of therapy, including an immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib or ixazomib), daratumumab, and glucocorticoids.
- For US subjects: Daratumumab combination regimen must be one of the prior lines of therapy (for this study, daratumumab plus corticosteroids will not be considered a combination regimen)
- For Non-US Subjects: Either daratumumab monotherapy or combination therapy is acceptable. Daratumumab monotherapy will be limited to approximately 20 percent of the total number of Phase 2 subjects.
- Measurable disease at Screening: Serum monoclonal protein of at least 1.0 g/dL (10g/L) 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, at least once during the screening period: ANC of at least 1000/μL (Subjects may use growth factor support to achieve ANC eligibility 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, platelet count of at least 30,000 mm³ (independent of transfusion for 2 weeks), hemoglobin of at least 8.0 g/dL (subjects may receive blood transfusion to achieve hemoglobin eligibility criteria), and total bilirubin not higher than 1.5 x ULN (subjects with Gilbert's Syndrome may have bilirubin higher 1.5 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 or equal to 3.
- 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.
- 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, localized prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen (PSA) levels off treatment, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Known HIV infection.
- Active hepatitis B or C infection
- Phase 1/Phase 2
- Study Type
- Intervention Model
- Single Group Assignment
- Primary Purpose
- None (Open Label)
ABT-199 Safety Expansion Cohort
Phase 2 Cohort
|Venetoclax-Dexamethasone Combination Expansion||
ABT-199 Dose Escalation Cohorts
- NCT ID