A Phase I Trial of ZIO-101 in Hematologic Cancers

Inclusion Criteria:

- Subjects must have relapsed/refractory leukemia or lymphoma for which no standard
therapies are anticipated to result in a durable remission. Relapsed/refractory
leukemia/lymphoma includes acute leukemia, chronic myeloproliferative disease,
chronic lymphoproliferative disease, multiple myeloma, and any type of lymphoma.
Subjects with poor-risk myelodysplasia (MDS) are also candidates for this protocol.
Poor risk MDS includes refractory anemia with excess blasts or excess blasts in
transformation, and chronic myelomonocytic leukemia.

- ECOG performance status of ≤ 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 serum or urine pregnancy test within 1 week prior to beginning
treatment on this trial. Nursing subjects are excluded. Sexually active men must also
use acceptable contraceptive methods. Pregnant and nursing subjects are excluded
because the effects of ZIO-101 on a fetus or nursing child are unknown.

- Must be able and willing to give written informed consent.

- Absent rapidly progressing disease, the interval from cancer therapy should be ≥ 3
weeks. Subjects receiving hydroxyurea should be on stable dose ≥ 7 days before
beginning treatment protocol. Persisting chronic toxicities from prior therapy must
be ≤ grade 1.

- Subjects must have the following clinical laboratory values:

- Serum creatinine ≤ 2 x the upper limit of normal

- Total bilirubin ≤ 2 x the upper limit of normal.

- Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) ≤ 3 x the
upper limit of normal.

- QTc interval < 450-470 mSec

Exclusion Criteria:

Subjects with any one of the following criteria will not be eligible for study
participation:

- Patients with indolent and stable myeloma, MDS or CLL not requiring therapy are not
eligible.

- Central nervous system (CNS) involvement with cancer.

- Uncontrolled active infection of any kind. Subjects with infections that are under
active treatment with antibiotics and whose infections are controlled may be entered
to the study.

- Active heart disease including myocardial infarction within previous 6 months;
symptomatic coronary artery disease; any type of chronic, ongoing arrhythmias; or
uncontrolled congestive heart failure.

- Concomitant therapy for hematologic cancer (except hydroxyurea).

- NYHA functional class ≥ 3, myocardial infarction ≤ 6 mo or uncontrolled cardiac
arrhythmia other than asymptomatic atrial fibrillation; QTc ≥450msec; AV-block ≥
grade-2 or Left Bundle Branch Block.