Clinical trial NCT01149915 (phase 1, status: completed)
Conditions: acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, high-risk myelodysplastic syndrome, chronic lymphocytic leukemia, advanced myelofibrosis
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C91.01, C91.02, C91.00, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C91.11, C91.12, C91.10
Drugs: th-302
SMILES: CN1C(COP(=O)(NCCBr)NCCBr)=CN=C1[N+]([O-])=O
Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age.

          -  Ability to understand the purposes and risks of the study and has signed a written
             informed consent form approved by the investigator's IRB/Ethics Committee.

          -  Relapsed/refractory leukemias for which no standard therapy options are anticipated to
             result in a durable remission.

          -  Acute myelogenous leukemia (AML) by WHO classification relapsed or refractory to
             standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo
             standard chemotherapy.

          -  Acute lymphoblastic leukemia (ALL) relapsed or refractory to standard chemotherapy;
             unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy.
             Philadelphia chromosome (Ph) positive ALL eligible if failed prior tyrosinekinase
             inhibitor therapy.

          -  Chronic myelogenous leukemia (CML) in accelerated or blast phase failing prior
             tyrosine kinase-containing therapy

          -  High-risk myelodysplastic syndrome (MDS) [i.e. refractory anemia with excess blasts
             (RAEB-1 or RAEB-2) by WHO classification] or chronic myelomonocytic leukemia (CMML)
             with >5% marrow blasts, relapsed or refractory to standard therapy

          -  Chronic lymphocytic leukemia (CLL) relapsed or refractory to standard therapy, not
             eligible for protocols of higher priority

          -  Advanced myelofibrosis (MF) resistant or refractory to standard therapy; or untreated
             with one of following features (1) hemoglobin < 10 g/dL, (2) platelet count < 100 x
             109/L, WBC < 4 or > 30 x 109/L, or splenomegaly ≥ 10 cm below left costal margin

          -  Age > 60 years with AML not candidates for or have refused standard chemotherapy,
             excluding subjects with acute promyelocytic leukemia (APL) or with favorable
             cytogenetic abnormalities [inv16, t(8;21)].

          -  ECOG performance status of less than or equal to 3

          -  Adequate organ function as indicated by the following laboratory assessments performed
             within 14 days prior to the first dose of study drug:

          -  Total bilirubin ≤ 1.5 times upper limit of normal (x ULN) (≤ 3 x ULN if due to
             leukemic involvement or Gilbert's syndrome).

          -  Aspartate aminotransferase or alanine aminotransferase ≤ 2.5 x ULN (≤ 5.0 x ULN if due
             to leukemic involvement)

          -  Serum creatinine ≤ 1.5 x ULN.

          -  All women of childbearing potential must have a negative serum pregnancy test and
             women and men subjects must agree to use effective means of contraception (surgical
             sterilization or the use or barrier contraception with either a condom or diaphragm in
             conjunction with spermicidal gel or an IUD) with their partner from entry into the
             study through 6 months after the last dose

        Exclusion Criteria:

          -  New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial
             infarction within 6 months prior to Day 1, or unstable arrhythmia

          -  Seizure disorders requiring anticonvulsant therapy

          -  Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the
             investigator any physiological state leading to hypoxemia

          -  Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without
             complete recovery

          -  Active uncontrolled infection

          -  Systemic chemotherapy (with the exception of hydroxyurea and/or steroids) within 14
             days (or within 5 half-lives for an investigational agent) prior to first dose of
             study drug, unless there is evidence of rapidly progressive disease. Concurrent
             therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is
             permitted.

          -  Known active infection with HIV, hepatitis B, or hepatitis C

          -  Patients who have exhibited allergic reactions to a similar structural compound,
             biological agent, or formulation (containing solutol and/or propylene glycol)

          -  Females who are pregnant or breast-feeding

          -  Concomitant disease or condition that could interfere with the conduct of the study,
             or that would, in the opinion of the investigator, pose an unacceptable risk to the
             subject in this study

          -  Unwillingness or inability to comply with the study protocol for any reason