Inclusion Criteria

• >= 18 years of age.

• Diagnoses:

  • 1a/1b - lymphoid malignancy;
  • 2a, Arm A - follicular lymphoma;
  • 2a, Arm B - mantle cell, peripheral or cutaneous T-cell lymphomas including mycosis fungoides and Sezary syndrome or other indolent B-cell lymphomas such as marginal zone lymphoma;
• Received at least 1 prior chemotherapy treatment regimen (P1a/1b) and relapsed or refractory disease (P2a).
• Eastern Cooperative Oncology Group (ECOG) score of <= 1.
• Magnetic Resonance Imaging (MRI)/computed tomography (CT) negative for subdural or epidural hematoma w/in 28 days prior to first dose, if clinically indicated.
• Stable dose of Selective serotonin reuptake inhibitors (SSRI) antidepressants for at least 21 days prior to 1st dose.

• Adequate bone marrow (BM) independent of any growth factor support (except with heavily infiltrated bone marrow (80% or more)):

  • Absolute Neutrophil Count (ANC) >= 1000/µL;
  • Platelets >= 100,000/mm3 (entry count must be independent of transfusion with in 14 days of Screening);
  • Hemoglobin >= 9.0/dL.

• Adequate coagulation, renal, and hepatic function:

  • Serum creatinine <= 2.0 mg/dL or calculated creatinine clearance >= 50 mL/min;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0 x Upper Limit of Normal (ULN);
  • Bilirubin <= 1.5 x ULN;
  • Gilbert's Syndrome may have a bilirubin > 1.5 x ULN;
  • Coagulation: Activated partial thromboplastin time (aPTT), Prothrombin Time (PT), not to exceed 1.2 x ULN
• Females must be surgically sterile, postmenopausal (at least 1 year), or negative results for a pregnancy test performed at Screening on a serum sample obtained with in 14 days prior to initial dose, and prior to dosing on a urine sample obtained on C1 D-3 (P1a) or Lead-in D1 (P1b, P2a) if > 7 days since serum results.
• Females not surgically sterile or postmenopausal (at least 1 year) and non-vasectomized males must practice birth control.

• P2a only: History of autologous stem cell transplant must be > 6 months post transplant with adequate BM independent of growth factor support per lab reference range at Screening as follows:

  • Absolute Neutrophil Count (ANC) >= 1,500/µL;
  • Platelets >= 125,000/mm3 (entry platelet count must be independent of transfusion with in 14 days of Screening);
  • Hemoglobin >= 10.0g/dL;
• Measurable disease by International Working Group (IWG)/National Cancer Institute- sponsored Working Group (NCI-WG) criteria.

• At least one of following for Pharmacodynamics (P2a):

  • archived diagnostic Formulin Fixed Paraffin Embedded (FFPE) tumor tissue with no intervening treatment since biopsy,
  • core needle biopsy of malignant lymph node, or
  • bone marrow aspirate or core positive for lymphoma.

Exclusion Criteria

• History of, or is, clinically suspicious for cancer-related Central Nervous System (CNS) disease, lymphoid or non-lymphoid.
• Undergone an allogeneic or autologous stem cell transplant.
• Underlying, predisposing condition of bleeding or currently exhibits signs of clinically significant bleeding.
• Recent history of non-chemotherapy induced thrombocytopenic associated bleeding with in 1 year prior to first dose.
• Active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
• Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions with in 1 year prior to first dose.
• Significant history of cardiovascular disease, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease.
• Females pregnant or breast-feeding.
• Positive for human immunodeficiency virus (HIV)
• History of other active malignancies with in the past 3 years (P1a/1b) or past 5 years (P2a), except adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent.
• Evidence of other clinically significant uncontrolled condition(s), including, but not limited to active systemic fungal infection; diagnosis of fever and neutropenia with in 1 week prior to study drug.
• Received steroid therapy with in 7 days prior to 1st dose of study drug for anti-neoplastic intent.
• Received any anti-cancer therapy, including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy, with in 14 days prior to first dose of study drug, or has not recovered to <Gr2 clinically significant AE(s) /toxicity(s) of the previous therapy.
• Received a biologic with in 30 days prior to first dose.
• Currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central venous catheter.
• Received aspirin with in 7 days prior to first dose and during ABT-263 administration.
• Consumed grapefruit or grapefruit products with in 3 days prior to first dose.
• P1a/1b only: Diagnosed with Posttransplant lymphoproliferative disorder (PTLD); Burkitt's, Burkitt-like, or HIV-associate lymphoma; lymphoblastic lymphoma/leukemia; or multiple myeloma.
• Subject has received CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 7 days prior to the administration of the first dose of ABT-263 (P2a).
• Subject had a prior significant toxicity from another Bcl-2 family protein inhibitor (P2a).

Extension Study Inclusion Criteria Phase 2a subjects who enter the Extension Study must continue to meet all Inclusion and Exclusion criteria, with the exception of Inclusion Criterion regarding measurable disease by International Working Group (IWG)/National Cancer Institute- sponsored Working Group (NCI-WG) criteria and Inclusion Criteria regarding laboratory parameters for hematology, coagulation, and chemistry. Subjects entering the Extension Study must also have stable lab values per applicable laboratory reference ranges.

In addition, subjects must also meet the following criteria:

• Subjects must meet the following hematology and coagulation lab criteria:

  • Platelet counts must be >= 25,000/mm3 (untransfused). Platelet counts <= 50,000/mm3 must be stable and monitored at an increased frequency at the discretion of the investigator.
  • Absolute Neutrophil count (ANC) >= 500/µL. ANC >= 500/µL and < 1,000/µL should be monitored at an increased frequency at the discretion of the investigator.
  • Hemoglobin of >= 8.0 g/dL.
  • aPTT, PT is not to exceed 1.2 x ULN.

• Chemistry values must not exceed Grade 2. Grade 2 chemistry labs should be monitored at an increased frequency at the discretion of the investigator. Subjects must meet the following chemistry criteria:

  • Serum creatinine <= 3.0 x the upper normal limit (ULN) of institution's normal range.
  • AST and ALT <= 5.0 x the upper normal limit (ULN) of institution's normal range.
  • Bilirubin <= 3.0 x ULN. Subjects with Gilbert's Syndrome may be allowed to have a Bilirubin > 3.0 x ULN based on a joint decision between the investigator and Abbott medical monitor.