Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

Inclusion Criteria:

1. Patients with histological confirmed relapsed or refractory leukemias for which no standard therapies are available that are expected to result in durable remissions. Eligible are patients with:

   * acute myeloid leukemia (AML) by WHO or FAB classification
   * acute lymphocytic leukemia (ALL)
   * adult T cell leukemia (ATL)
   * chronic myeloid leukemia in blast crisis (CML-BP) having failed Bcr-Abl specific kinase inhibitors (e.g. imatinib and/or dasatinib)
   * chronic lymphocytic leukemia (CLL)
   * poor-risk myelodysplastic syndrome (MDS) \[by WHO \>10% blasts or IPSS groups: Int-2, high\]
   * chronic myelomonocytic leukemia (CMML)
2. ECOG performance status of 0-1
3. Negative pregnancy test within 7 days of start of study drug NOTE: Men and women of child-producing potential must use effective contraceptive methods during the study (e.g. abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device)
4. Written informed consent
5. In the absence of rapidly progressing disease, the interval from prior therapies to time of study drug administration should be a minimum of 3 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent chronic toxicities from prior chemotherapy must not be greater than grade 1
6. Age greater than or equal to 18 years
7. Patients must have the following clinical laboratory values:

   * Serum creatinine less than or equal to 2.0 mg/dl or creatinine clearance greater than 50ml/hr
   * Total bilirubin less than or equal to 1.5x the upper limit of normal unless considered due to Gilbert's syndrome
   * Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) less than or equal to 3x the upper limit of normal unless considered due to organ leukemic involvement

Exclusion Criteria:

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

1. Uncontrolled intercurrent illness including, but not limited to,

   * uncontrolled infection,
   * myocardial infarction within previous 3 months,
   * symptomatic congestive heart failure (New York Heart Association Class III, IV),
   * symptomatic coronary artery disease
   * cardiac arrhythmia not controlled by medication NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible
2. Psychiatric illness/social situations that would limit compliance with study requirements or unwillingness or inability to comply with procedures required in this protocol
3. Patients receiving any other standard or investigational treatment for their leukemia NOTE: Hydroxyurea is allowed prior to study drug start and for the first 7 days of therapy
4. Pregnant and nursing patients are excluded. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1
6. Patients with known CNS disease
7. History of allergic reactions attributed to compounds of similar chemical or biological composition to Terameprocol (EM-1421) or excipients