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).