Safety Study of CAT-8015 Immunotoxin in Patients With CLL, PLL or SLL With Advance Disease

OUTLINE: Patients receive CAT-8015 IV over 30 minutes on days 1, 3, and 5 followed by rest.
Treatment repeats every 4 weeks for up to a total of 10 courses in the absence of dose
limiting toxicity, complete response or disease progression. Patients are followed at 1, 3,
6,12,15,18, 21, 24 months following the start of the last treatment cycle.

Cohorts of 3-6 patients each will receive escalating doses of recombinant CAT-8015 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that
at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is
determined, between16 to 25 new patients will be added to the MTD cohort depending on how
well the CAT-8015 is tolerated.

INCLUSION CRITERIA:

DISEASE CHARACTERISTICS:

- Confirmed diagnosis of B-cell leukemia (CLL, PLL or SLL)

- Measurable disease

- 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.

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 direct bilirubin:

- ≥ Grade 2, unless bilirun 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, corticosteriods (except stable doses of prednisone), whole
body electron beam radiation therapy, hormonal, biologic 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