- 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
- 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.
- Subjects must be aged 18 years or older.
- Women of childbearing potential must agree not to become pregnant for the duration of
- 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 109/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
- 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
- Known central nervous system (CNS) involvement by malignancy.
- Untreated autoimmunity such as autoimmune hemolytic anemia, or immune
- 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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: 70 Years
Eligible Gender: Both