Hu8F4 in Treating Patients With Advanced Hematologic Malignancies

PRIMARY OBJECTIVES:

I. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of Hu8F4
when administered intravenously in patients with leukemia or myelodysplastic syndrome (MDS).

II. To determine the pharmacokinetics (PK) of Hu8F4 following study drug administration.

SECONDARY OBJECTIVES:

I. To observe the anti-leukemia effects of Hu8F4 in patients with leukemias and MDS.

II. To measure the overall survival, disease-free survival and event-free survival of
patients with leukemias or MDS treated with Hu8F4.

OUTLINE: This is a dose-escalation study.

Patients receive anti-PR1/HLA-A2 monoclonal antibody Hu8F4 intravenously (IV) over 60 minutes
on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Inclusion Criteria:

- Patients with any of the following diagnoses are eligible: 1) high-risk MDS (i.e.
refractory anemia with excess blasts [RAEB-1 or RAEB-2] by World Health Organization
[WHO] classification, or any WHO subset with International Prognostic Scoring System
[IPSS] intermediate-2 or high, or any patients that has failed prior therapy with
hypomethylating agents); 2) chronic myelomonocytic leukemia (CMML); 3) acute myeloid
leukemia (AML) by WHO classification; 4) chronic myeloid leukemia in blast phase
(CML-BP); 5) myelofibrosis with high-risk features (e.g., accelerated phase disease
-10-19% blasts in peripheral blood or bone marrow-, or with Dynamic International
Prognostic Scoring System [DIPSS]-plus high risk score)

- Patients must have relapsed/refractory disease; patients with secondary AML (including
those progressing from MDS or myeloproliferative neoplasm [MPN], and those with AML
secondary to chemotherapy or radiotherapy for other malignancies) are eligible whether
they have received prior therapy for AML or not; patients with high-risk myelofibrosis
are also eligible regardless of whether they have received prior therapy or not

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically
sterile) must use acceptable contraceptive methods (abstinence, intrauterine device
[IUD], oral contraceptive or double barrier device), and must have a negative urine
pregnancy test within 2 weeks prior to beginning treatment on this trial; nursing
patients are excluded; sexually active men must also use acceptable contraceptive
methods for the duration of time on study

- Patients must have human leukocyte antigen (HLA)-A2 phenotype

- Must be able and willing to give written informed consent

- In the absence of rapidly progressing disease, the interval from prior treatment to
time of study drug administration should be at least 2 weeks for cytotoxic agents, or
at least 5 half-lives for noncytotoxic agents; exceptions are 1) hydroxyurea that
requires no washout prior to the start of Hu8F4, and 2) up to 2 doses of single-agent
cytarabine (up to 3 grams/m^2) given for palliative purposes for which a washout of
>/=5 days is required

- Clinically significant toxicities from prior chemotherapy must not be greater than
grade 1

- Serum creatinine =< 1.5 x the upper limit of normal

- Total bilirubin =< 1.5 x the upper limit of normal unless considered due to Gilbert's
syndrome

- Alanine aminotransferase (ALT) =< 3 x the upper limit of normal unless considered due
to leukemic involvement

Exclusion Criteria:

- Uncontrolled intercurrent illness including, but not limited to uncontrolled infection
(patients must have no temperature >= 38.3 degree Celsius [C] due to infection for at
least 48 hrs to consider an infection controlled), psychiatric illness that would
limit compliance with study requirements, or active heart disease including confirmed
myocardial infarction within previous 3 months, symptomatic coronary artery disease,
clinically significant arrhythmias not controlled by medication, or uncontrolled
congestive heart failure New York (NY) Heart Association class III or IV

- Patients with current active malignancies or any remission for < 24 months, except
patients with carcinoma in situ or with non-melanoma skin cancer who may have active
disease or be in remission for less than 6 months

- Patients receiving any other standard or investigational treatment for their
hematologic malignancy other than supportive care

- Patients who have had any major surgical procedure within 14 days of day 1

- Patients with known central nervous system infiltration with leukemia

- Patients who received a stem cell transplant =< 12 months from the start of therapy

- Patients with active graft versus host disease (GVHD), or receiving therapy for GVHD

- Patients with known active central nervous system (CNS) disease; patients with history
of active CNS disease should have at least two negative spinal fluid evaluations
before being considered eligible