A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia

Study start date: February 29, 2004

* INCLUSION CRITERIA: Patients must have histopathological evidence of CD25+ CLL or prolymphocytic leukemia (PLL) confirmed by the NIH pathology department. This requires that at least 50% of the peripheral malignant lymphocytes be CD25 positive by fluorescence activated cell sorting (FACS) with anti-CD25 antibody. Positive expression in a FACS assay is defined as more than 2 times the mean fluorescence intensity (MFI) of the control antibody by FACS, or greater than 400 CD25 sites/cell by FACS or radiolabeled binding assay. In the three stage modified Rai system, patients must be intermediate or high risk. This means they must have circulating CLL cells and at least one of the following: lymphadenopathy, splenomegaly, hepatomegaly, anemia (Hgb less than 11g/dL), or thrombocytopenia (Plt less than 100,000/ul). Patients must have had progressive disease after prior standard therapy containing either a purine analog or an alkylating agent. Patients must not have received systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic steroids (except stable doses of Prednisone less than or equal to 20 mg/day) within 4 weeks of enrollment. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2. At least 18 years old. Patients must be able to understand and give informed consent. Female patients of childbearing potential must have a negative pregnancy test and all patients must use effective contraception (a barrier form of contraception). The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must each be less than or equal to 2.5-times the upper limits of normal. Albumin must be greater than or equal to 3.0 gm/dL. Total bilirubin must be less than or equal to 2.2 mg/dL except in patients with Gilbert's syndrome (as defined by greater than 80% unconjugated bilirubin) it must be less than 5 mg/dl. The creatinine must be less than or equal to 1.4 mg/dL or the creatinine clearance must be greater than or equal to 50 ml/min as measured from a 24-hour urine collection. Patients should not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. EXCLUSION CRITERIA: Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or anti-mouse-lgG antibodies. No patient whose serum neutralizes greater than 75% of the activity of 1 micro g/mL of LMB-2 will be treated. Patients who received LMB-2 on another trial. Monoclonal antibody therapy within 12 weeks of enrollment. Patients who are pregnant or breast-feeding. Patients who are human immunodeficiency virus (HIV) positive. Patients who have hepatitis C or chronic liver disease. Patients would not be excluded for hepatitis B surface antigen positivity if on Lamivudine. Patients receiving warfarin for anticoagulation. Patients with a left ventricular ejection fraction of less than the institutional lower limit of normal. Patients with a carbon monoxide diffusing capacity (DLCO) less than 55% of normal or an forced expiratory volume 1 (FEV1) less than 60% of normal. Patients who have active cancer requiring treatment.