A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Patient With Relapsed or Refractory Hairy Cell Leukemia (HCL)

Inclusion Criteria

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