A Phase I, Two-part Study to Determine the Recommended Dose and Evaluate the Safety and Tolerability of a Novel Oral Arsenic Trioxide Formulation (ORH-2014) in Subjects With Advanced Hematological Disorders

Inclusion Criteria:

- Female and male subjects ≥18 years of age with one of the following:

- Relapsed or refractory acute myelocytic leukemia (AML) with nucleophosmin-1
(NPM1) mutations and no available therapies.

- Relapsed or refractory acute promyelocytic leukemia (APL), with no available
therapies. Note: Prior exposure to arsenic trioxide is allowed; however, subjects
who have failed arsenic trioxide within the last 12 months are not allowed.

- Relapsed or refractory myelodysplastic syndrome (MDS), International Prognostic
Scoring System intermediate or high-risk, with no available therapies

- Relapsed or refractory chronic myelomonocytic leukemia (CMML), and other
MDS/myeloproliferative neoplasm (MPN) overlap syndromes, with no available
therapies

- Relapsed or refractory mantle cell lymphoma (MCL) with no adequate therapies.

- Negative pregnancy test at the Screening visit for women of childbearing potential and
willingness to use adequate birth control

- Not willing to undergo, not a candidate for, or not having a donor for immediate
(within 3 months from the Screening date) bone marrow transplantation.

Exclusion Criteria:

- Eastern Cooperative Oncology Group performance status of ≥3;

- Absolute myeloblast count ≥20,000/mm^3;

- Administration of any antineoplastic therapy within 5 half-lives of the antineoplastic
therapy before the first dose of ORH-2014, with the exception of hydroxyurea that
should be discontinued 1 day prior to the first dose of ORH-2014

- Presence of any remaining toxicities due to previous chemotherapy

- Participation in other clinical trials within at least 2 weeks of the first ORH-2014
dose;

- Clinical evidence of active central nervous system leukemia;

- Active and uncontrolled infection

- Major surgery within 2 weeks prior to trial entry;

- Liver function tests above the following limits at Screening: total bilirubin >1.5 x
upper limit of normal (ULN) unless related to Gilbert's syndrome or hemolysis;
aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x ULN; for
subjects with liver involvement, AST and/or ALT >5 x ULN;

- Serum creatinine >1.5 x ULN and/or creatinine clearance or estimated glomerular
filtration rate <30 mL/min

- Impaired cardiac function

- Myocardial infarction of unstable angina within 6 months prior to the planned start
date of study drug.