UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia

INCLUSION CRITERIA: * Clinical and phenotypic verification of B cell CLL and measurable disease. Immunophenotyping of the leukemic cells must demonstrate a monoclonal B cell population with immunophenotype consistent with CLL. * Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of therapy, or a 50% increase of baseline disease measurements after achieving a clinical response. * Not amenable to approved therapies. * Prior Therapy: Must have progressed after purine-analog or alkylator based therapy, or be considered inappropriate for chemo-immunotherapy due to one of the following: * Del 17p, which is associated with poor response to chemo-immunotherapy, or * Age greater than 70, or * Age greater than 65 with one of the following: * Grade ≥ 3 neutropenia, anemia, or thrombocytopenia attributable to cumulative myelotoxicity from prior administration of cytotoxic agents (as documented by bone marrow biopsy obtained since last prior therapy), or * Clinically apparent autoimmune cytopenia which may be exacerbated by fludarabine therapy, or * Estimated creatinine clearance (eCCr) \<70 mL/min (as determined by the Cockcroft-Gault method), or * Eastern Cooperative Oncology Group (ECOG) performance status greater than 0. * Has recovered from the toxic effects of prior therapy to their clinical baseline. * Women of childbearing potential must agree not to become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 10 weeks after the final dose of cirmtuzumab. * Subjects must have at least one of the following indications for treatment: * Symptomatic or progressive splenomegaly; * Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy; * Progressive anemia (hemoglobin ≤ 11 g/dL); * Progressive thrombocytopenia (platelets ≤ 100 x 10\^9/L); * Weight loss \> 10% body weight over the preceding 6 month period; * Fatigue attributable to CLL; * Fever or night sweats for \> 2 weeks without evidence of infection; * Progressive lymphocytosis with an increase of \> 50% over a 2-month period or an anticipated doubling time of less than 12 months. * Subjects must have an ECOG performance status of 0-2. * Adequate hematologic function * Adequate renal function * Adequate hepatic function * Adequate coagulation tests EXCLUSION CRITERIA: * Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. * Patients who are currently receiving another investigational agent are excluded. * Patients who have had chemotherapy (e.g., purine analogues, alkylating agents), immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of initiation of UC-961 or at any time during the study. * Patients who have had prior (within 8 weeks of initiation of UC-961) or concurrent antibody therapy directed against CLL (i.e., Rituxan® and Campath®). * Current infection requiring parenteral antibiotics. * Active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). * Concurrent malignancy or prior malignancy within the previous 3 years (other than completely resected carcinoma in situ, prostate cancer, or localized non-melanoma skin cancer). * Known central nervous system (CNS) involvement by malignancy. * Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia. * Uncompensated hypothyroidism (defined as thyroid-stimulating hormone (TSH) greater than 2x upper limit of normal not treated with replacement hormone). * Presence of more than 55% pro-lymphocytes in peripheral blood. Patients with Richter's transformation are not excluded. * Insufficient recovery from surgical-related trauma or wound healing. * Impaired cardiac function including any of the following: * Myocardial infarction within 6 months of starting study drug; * A past medical history of clinically significant ECG abnormalities, including QTc 481 milliseconds or greater; * Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).