| Eligibility |
Inclusion Criteria:
1. Diagnosis of:
- Relapsed or refractory AML (refractory to a standard anthracycline-based
induction regimen or a hypomethylating agent for patients unfit for intensive
chemotherapy or for whom no standard or curative therapy exists),
- ALL,
- Acute biphenotypic leukemia (assigned to the appropriate group by the treating
physician by documented analysis of relevant laboratory values and
pathology/cytogenetics),
- Advanced MDS defined as =5% bone marrow blasts or =2% blasts in the peripheral
blood (including patients who have progressed following treatment with
hypomethylating agents),
- Advanced MPN (excluding patients with ET, PV, or low risk MF), and MDS/MPN
overlap syndrome with =5% bone marrow blasts or =2% blasts in the peripheral
blood, or
- Advanced CML after failure/progression of at least 3 prior TKIs
2. Age =18 years
3. No prior antineoplastic drug therapy for at least 14 days, with the exception of
hydroxyurea, prior to starting OTS167. Patients with rapidly proliferative disease may
continue to receive hydroxyurea
4. Patients refractory to all approved therapies or for which no approved or conventional
therapies are available
5. Patients with a diagnosis of advanced CML must have been treated with 3 prior TKIs,
and the last therapy must have been discontinued at least 14 days prior to starting
OTS167
6. Adequate organ function as defined below:
- Liver function (total bilirubin <2 mg/dL and aspartate aminotransferase and/or
alanine aminotransferase <3 × upper limit of normal (ULN) or <5 × ULN if related
to leukemic involvement)
- Renal function (creatinine <1.5 × ULN)
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
8. Negative urine pregnancy test within 1 week prior to Cycle 1 Day 1 for each woman of
childbearing potential
9. Able to understand the potential risks, benefits, and requirements of the study and
are willing to provide informed consent; an informed consent form (ICF) for this study
that is signed by the patient or his/her legally authorized representative is required
prior to enrollment
Exclusion Criteria:
1. Pregnant or breastfeeding patients (pregnant and breastfeeding women are excluded from
this study because the agents used in this study may have unknown or unrecognized
potential for teratogenic or abortifacient effects). Patients of childbearing
potential must consent and agree to practice documented (type) adequate contraception
during the course of on study treatment.
2. Evidence of any form of active, uncontrolled, bacterial, viral (including hepatitis A,
B, or C or known human immunodeficiency virus [HIV] seropositivity), or fungal
infection. Patients who are positive for hepatitis B core antibody, hepatitis B
surface antigen, or hepatitis C antibody must have a negative polymerase chain
reaction (PCR) result before enrollment; those who are PCR-positive will be excluded.
Evidence of congestive heart failure (New York Heart Association Class III or IV);
myocardial infarction or stroke within 6 months; unstable angina; uncontrolled or
unstable/medically important cardiac arrhythmia; prolonged QT interval corrected for
heart rate (QTc) >450 msec (males) or >470 msec (females); uncontrolled epilepsy;
uncontrolled bleeding; recent major surgical procedures within 30 days before Cycle 1
Day 1 without full recovery from the same; or any other serious comorbid medical
condition that would preclude investigational study treatment
3. Any psychiatric illness/social situations that would limit compliance with study
requirements
4. Documented hypersensitivity to any of the components of OTS167 or supportive care
medicaments
5. Central nervous system (CNS) leukemia
6. MPN patients with ET, PV, or low risk MF
7. Women of childbearing potential and men must agree prior to study entry to use
appropriate contraception for the duration of study participation and until 30 days
after receipt of the last dose of study drug
8. Documented concurrent malignancy. Exceptions include cervical carcinoma in-situ,
non-melanoma skin cancer (basal and squamous cell carcinoma), localized prostate
cancer (Gleason score <6), and resected melanoma-in-situ. Other localized solid tumors
in situ and other low risk cancers may also be exempt after discussion with the
Sponsor Medical Monitor.
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