Study subjects may enroll who have relapsed or treatment refractory CLL, PLL or SLL as defined by the following inclusion and exclusion criteria:
INCLUSION CRITERIA:
Subjects must meet all of the following criteria to be eligible to participate in the study:
1. Confirmed diagnosis of B-cell leukemia (CLL, PLL or SLL).
2. Measurable disease.
3. Disease characteristics: Patients with chronic lymphocytic leukemia (CLL), or small lymphocytic lymphoma (SLL) are eligible if they have failed 2 or more prior courses of standard chemotherapy and/or biologic therapy (e.g. Rituxan) and if treatment for progressive disease is medically indicated. Patients with prolymphocytic leukemia (PLL) will be eligible if they have failed at least one prior standard chemotherapeutic regimen. Medical indications for treatment include progressive disease-related symptoms, progressive cytopenias due to marrow involvement, progressive or painful splenomegaly or adenopathy, rapidly increasing lymphocytosis, autoimmune hemolytic anemia or thrombocytopenia and increased frequency of infections.
4. ECOG performance status of 0-2.
5. Patients with other cancers who meet eligibility criteria and have had less than 5 years of disease-free survival will be considered on a case-by-case basis.
6. Life expectancy of greater than 6 months, as assessed by the principal investigator.
7. Must be able to understand and sign informed consent.
8. Must be at least 18 years old.
9. Female and male patients agree to use an approved method of contraception during the study.
EXCLUSION CRITERIA:
Subjects meeting any of the following criteria are not eligible for participation in the study:
1. Hepatic function: serum transaminases (either ALT or AST) or bilirubin greater than or equal to Grade 2, unless bilirubin is due to Gilbert's disease.
2. Renal function: serum creatinine clearance less than or equal to 60mL/min as estimated by Cockroft-Gault formula.
3. Hematologic function:
-The ANC less than 1000/cmm, or platelet count less than 50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy).
-A patient will not be excluded because of pancytopenia greater than or equal to Grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies.
-Baseline coagulopathy greater than or equal to grade 3 unless due to anticoagulant therapy.
4. Pulmonary function: Patients with less than 50% of predicted forced expiratory volume (FEV1) or less than 50% of predicted diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin concentration and alveolar volume. Note: Patients with no prior history of pulmonary illness are not required to have PFTs. FEV1 will be assessed after bronchodilator therapy.
5. History of allogeneic bone marrow transplant.
6. Documented and ongoing central nervous system involvement with their malignant disease (history of CNS involvement is not an exclusion criterion).
7. Pregnant or breast-feeding females.
8. Patients whose plasma contains either a significant level of antibody to CAT-8015 as measured by ELISA, or antibody that neutralizes the binding of CAT-8015 to CD22 as measured by a competition ELISA.
9. Recent prior therapy:
-Cytotoxic chemotherapy, corticosteroids (except stable doses of prednisone), whole body electron beam radiation therapy, hormonal, biologic or other standard or any investigational therapy of the malignancy for 3 weeks prior to entry into the trial.
-Less than or equal to 1 month prior monoclonal antibody therapy (i.e. rituximab).
-Patients who are receiving or have received radiation therapy less than 3 weeks prior to study entry will not be excluded providing the volume of bone marrow treated is less than 10% and also the patient has measurable disease outside the radiation port.
-Any history of prior pseudomonas-exotoxin immunotoxin administration.
10. HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs).
11. Hepatitis B surface antigen positive.
12. Uncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/20/2008