A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies

Inclusion Criteria:

Refractory or relapsed chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) or non-Hodgkin lymphoma (NHL) (including those of T cell origin)
Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2
Negative pregnancy test (women of childbearing potential)

Hematologic function, as follows (no platelet transfusion within 2 weeks and no RBC transfusion within 4 days before the first dose of study drug)

Absolute neutrophil count (ANC) ≥ 1,000/μL
Platelets ≥ 75,000/μL
Hemoglobin ≥ 8 g/dL (may be transfused ≥ 5 days)
Renal function: serum creatinine ≤ 2.0 mg/dL and estimated creatinine clearance of ≥ 45 mL/min by the Cockcroft-Gault equation
Direct bilirubin ≤ 1.5 x upper limit of normal (ULN)
Serum albumin ≥ 2.5 g/dL
Aspartate aminotransferase (AST) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN
Alanine aminotransferase (ALT) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN
Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 weeks after termination of study therapy

Exclusion Criteria:

Preexisting sensory and/or motor neuropathy Grade ≥ 2
Small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 2 weeks before first dose of study drug
Radioimmunotherapy within 4 weeks before first dose of study drug
Use of any investigational drug (including marketed drugs not approved for this indication) within 14 days prior to the first dose of study drug
Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 2 weeks before the first dose of study drug (See Appendix F for list of excluded drugs)
Anti Graft-Versus-Host Disease (GVHD) therapy within 12 weeks before the first dose of study drug
Platelet transfusion within 2 weeks and RBC transfusion within 4 days before the first dose of study drug
Known central nervous system (CNS) disease

History of other primary malignancy (including myeloid malignancy, e.g., myelodysplastic syndrome), unless

Curatively resected nonmelanomatous skin cancer
Other malignancy curatively treated with no known active disease present and no systemic treatment administered for 3 years before the first dose of study drug
Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
Women who are pregnant or lactating
Known HIV positive or AIDS
Positive Hepatitis B surface antigen test
Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy

Known sensitivity to any of the components of the investigational product AGS67E:

AGS67E
L-Histidine
α-trehalose dihydrate or
polysorbate 20
History of thromboembolic events (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) ≤ 2 weeks before the first dose of study drug and/or clinical diffuse intravascular coagulation (DIC)
Active infection requiring treatment ≤7 days before the first dose of study drug
Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
Any medical, psychiatric, addictive or other disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.