Study Evaluating ABT-199 in Participants With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

* ECOG (Eastern Cooperative Oncology Group) performance score of 1 or 0. Participants in the Phase 2 portion: ECOG performance score of 2, 1, or 0.
* Diagnosis of multiple myeloma (MM) 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, participants must have been previously treated with a proteasome inhibitor (e.g., bortezomib) and an immunomodulatory agent (e.g., thalidomide, lenalidomide).
  * For Venetoclax-Dexamethasone Combination, participants must have 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, participants 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 Therapeutic Area MD). Participants must have evidence of disease progression on or within 60 days of last dose of most recent previous treatment based on International Myeloma Working Group (IMWG) criteria AND 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 participants: 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 participants: Either daratumumab monotherapy or combination therapy is acceptable. Daratumumab monotherapy will be limited to approximately 20 percent of the total number of Phase 2 participants.
* Measurable disease at Screening:

  * Serum monoclonal protein of at least 1.0 g/dL (10g/L) by protein electrophoresis.
  * At least 200 mg of monoclonal protein in the urine on 24-hr electrophoresis.
  * Serum immunoglobulin free light chain of at least 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.
* Participants 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:

  * Absolute Neutrophil Count (ANC) of at least 1000/μL (Participants may use growth factor support to achieve ANC eligibility criteria).
  * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) not higher than 3 x Upper Limit of Normal Range (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 (participants may receive blood transfusion to achieve hemoglobin eligibility criteria).
  * Total bilirubin not higher than 1.5 x ULN (Participants with Gilbert's Syndrome may have bilirubin higher than 1.5 x ULN).

Exclusion Criteria:

* Exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to:

  * Acute infection within 14 days prior to first dose of study drug requiring antibiotic, antifungal, or antiviral therapy.
  * Diagnosis of fever and neutropenia within 1 week prior to first dose of study drug.
* Cardiovascular disability status of New York Heart Association Class ≥ 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 Human Immunodeficiency Viral (HIV) infection.
* Active hepatitis B or C infection.