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) 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).