Safety Study of CAT-8015 Immunooxin in Patients With HCL With Advance Disease

INCLUSION CRITERIA:

DISEASE CHARACTERISTICS:

   - Confirmed diagnosis of hairy cell leukemia

   - Measurable disease

At least one of the following indications for treatment:

   - Neutropenia (ANC <1000 cells/µL)

   - Anemia (Hgb <10g/dL)

   - Thrombocytopenia (Plt <100,000/µL)

   - An absolute lymphocyte count of >20,000 cells/µL, or

   - Symptomatic splenomegaly

   - Patient's must have had at least 2 prior systemic therapies. There must have been at
   least 2 prior courses of purine analog, or 1 if the response to this course lasted <2
   years, or if the patient had unacceptable toxicity to purine analog.

PATIENT CHARACTERISTICS:

Performance status • ECOG 0-2

Life expectancy

• Life expectancy of greater than 6 months, as assessed by the principal investigator

Other

   - 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

   - Ability to understand and sign informed consent

   - Female and male patients agree to use an approved method of contraception during the
   study

EXCLUSION CRITERIA:

   - Documented and ongoing central nervous system involvement with their malignant disease
   (history of CNS involvement is not an exclusion criterion)

   - History of bone marrow transplant

   - Pregnant or breast-feeding females

   - 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.

   - HIV positive serology (due to increased risk of severe infection and unknown
   interaction of CAT-8015 with antiretroviral drugs)

   - Hepatitis B surface antigen positive

   - 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

Hepatic function: serum transaminases (either ALT or AST) or bilirubin:

• ≥ Grade 2, unless bilirubin is due to Gilbert's disease

Renal function: serum creatinine clearance ≤60mL/min as estimated by Cockroft-Gault formula

Hematologic function:

   - The ANC <1000/cmm, or platelet count <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)

   - Baseline coagulopathy > grade 3 unless due to anticoagulant therapy

   - A patient will not be excluded because of pancytopenia ≥ Grade 3, or erythropoietin
   dependence, if it is due to disease, based on the results of bone marrow studies

Pulmonary function:

• Patients with < 50% of predicted forced expiratory volume (FEV1) or <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 following bronchodilator therapy.

Recent prior therapy:

   - Cytotoxic chemotherapy (except stable doses of prednisone), whole body electron beam
   radiation therapy, interferon, retinoids or other systemic therapy, or investigational
   therapy of the malignancy for 3 weeks prior to entry into the trial

   - Less than or equal to < 3 months prior monoclonal antibody therapy (i.e. rituximab)

   - Patients who have received or are receiving radiation therapy less than 3 weeks prior
   to study entry will be 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 pseudomonas-exotoxin (PE) immunotoxin administration