Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Background:

- Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2% of all leukemias,
or approximately 900 of the 44,000 new cases of leukemia/year in the US

- Over the last two decades, immunotoxin research has accumulated to support a role for
CD22-targeted therapy in the treatment of HCL.

- Moxetumomab pasudotox is a recombinant immunotoxin containing an Fv fragment of an
anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin.

- Moxetumomab pasudotox has demonstrated a high complete response (CR) rate in patients
with chemoresistant HCL and has shown activity in pediatric acute lymphoblastic leukemia
as well.

- Modification of the structure of moxetumomab pasudotox has greatly improved binding and
cytotoxicity toward CD22 expressing malignant cells compared to the precursor molecule.
Preclinical and clinical studies have demonstrated that this increase in binding
affinity results in improved antitumor activity and tolerability

- Currently there are no approved agents with significant efficacy for HCL patients after
failure of standard therapy

Design:

- This is a multicenter, single-arm study of moxetumomab pasudotox in patients with
relapsed/refractory hairy cell leukemia.

- 77 patients will be enrolled to receive moxetumomab pasudotox intravenously (IV) on days
1, 3 and 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression,
unacceptable toxicity occurs, the subject begins alternate therapy, or documented CR
(for subjects who have no assessable minimal residual disease and not to exceed 6
cycles). If less than or equal to 2 of the first 25 patients do not achieve durable CR,
no additional patients will be accrued.

- The overall IRB accrual ceiling is currently set at 80 to allow for a small number of
patients that cannot be assessed for response.

- INCLUSION CRITERIA:

- Patients must have histologically confirmed hairy cell leukemia or hairy cell leukemia
variant .with a need for therapy

- Patients must be Pseudomonas-immunotoxin naive

- Patients must have had at least 2 prior purine analogs, or at least 1 course of purine
analog and 1 of either rituximab or BRAF inhibitor.

- Men or women age greater than or equal to 18 years.

- ECOG performance status less than or equal to 2.

- Patients must have adequate organ function

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

- Patients with clinically significant ophthalmologic findings during screening

- Pregnant or breastfeeding females.

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

- Active second malignancy requiring treatment other than minor resection of indolent
cancers like basal cell and squamous skin cancers

- HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count
of greater than 200.

- History of allogeneic bone marrow transplant.

- Patients with history of both thromboembolism and known congenital hypercoagulable
conditions.

- Uncontrolled pulmonary infection, pulmonary edema.

- Adequate oxygen saturation

- Radioimmunotherapy within 2 years prior to enrollment in study.

- Adequate hematologic function

- Adequate lung function

- Patients with history of thrombotic microangiopathy or thrombotic microangiopathy /
hemolytic uremic syndrome

- Patients with QTc interval (Friderica) elevation > 500 msec based on at least 2
separate 12-lead ECGs

- Patient on high dose estrogen

- Patients with clinical evidence of disseminated intravascular coagulation