A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia

Inclusion Criteria

- INCLUSION CRITERIA:

- Patients must have histologically confirmed hairy cell leukemia with a need for
therapy based on at least one of the following criteria:

neutrophils less than 1000/mm(3)

platelets less than 100,000/mm(3)

hemoglobin less than 10 g/dL)

symptomatic splenomegaly.

- Patients must be Pseudomonas-immunotoxin na ve

- Patients must have had at least 2 prior systemic therapies, including at least 2
prior courses of purine analog, or 1 if the response to this course lasted less than
1 year, or if the patient had unacceptable toxicity to purine analog.

- Men or women age greater than or equal to 18 years. Because this disease does not
generally occur in children, children are excluded from this study, but will be
eligible for future pediatric trials in other indications.

- ECOG performance status less than or equal to 2.

- The effects of moxetumomab pasudotox on the developing human fetus are unknown. For
this reason, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation, and 4 months after
completion of moxetumomab pasudotox administration. Should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately.

- Patients must have adequate organ function as defined below:

- total bilirubin less than or equal to 1.5 mg/dL, unless consistent with Gilbert's
(ratio between total and direct bilirubin greater than 5)

- AST and ALT less than or equal to 3 times upper limit of normal (ULN)

- alkaline phosphatase less than or equal to 2.5 ULN

- serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than
or equal to 60 mL/min as estimated by the Cockcroft-Gault equation

- Prothrombin time/INR or partial thromboplastin time less 2.5 ULN, fibrinogen greater
than or equal to 0.5 LLN; if on warfarin, INR less than 3.5, if on any other
anticoagulation, PT less than 2.5 times baseline

- Ability to understand and the willingness to sign a written informed consent
document.

- Life expectancy greater than or equal to 6 months

EXCLUSION CRITERIA

- Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks
prior to entering the study.

- Patients who are receiving any other investigational agents.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

- Patients with clinically significant opthalmologic findings during screening

- Pregnant or breastfeeding females. The effects of moxetumomab pasudotox on the
developing fetus are unknown. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with
moxetumomab pasudotox breastfeeding should be discontinued if the mother is treated
with moxetumomab pasudotox

- Positive for Hepatitis B surface antigen unless the patient is on Lamivudine or
Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.

- Lymph nodes greater than 4cm or prior splenectomy

- Active second malignancy requiring treatment

- 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.

- HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count
of greater than 200. Otherwise, there may be increased risk of lethal infections when
temporarily suppressing normal B-cells.

- History of allogeneic bone marrow transplant

- Uncontrolled, symptomatic, intercurrent illness including but not limited to:
infections requiring systemic antibiotics, congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, psychiatric illness, malaria infection, or social
situations that would limit compliance with study requirements

- Uncontrolled pulmonary infection, pulmonary edema

- Oxygen saturation at rest less than 88% measured by pulse oximetry or PaO (2) less
than or equal to 55 mm Hg

- Serum albumin less than 2 g/dL

- Radioimmunotherapy within 2 years prior to enrollment in study

- ANC less than 1000/mm(3), or platelet count less than 50,000/mm(3), if these
cytopenias are not judged by the investigator to be due to underlying disease (ie,
potentially reversible with antineoplastic 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

- 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.

- Patients with history of thrombotic microangiopathy or TTP-HUS.

- Patients with QTc elevation greater than grade 1.