A Study to Evaluate the Pharmacokinetics, Safety,and Efficacy of Omacetaxine Given Subcutaneously as a Fixed Dose in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML) (Referred to as the SYNSINCT Study)

Because the trial was not feasible due to the inability to accrue additional clinical study
sites and enroll an adequate number of subjects, the FDA released the sponsor from the
postmarketing requirement on 13 November 2017 and the study was stopped prematurely.
Therefore, the study did not progress to the Phase 2 portion.

Inclusion Criteria:

- The patient has a confirmed diagnosis of Philadelphia chromosome (Ph) positive chronic
myelogenous leukemia in either CP or AP. Accelerated phase will be defined as disease
having 1 of the following: ≥15% to <30% blasts in peripheral blood or bone marrow;
≥30% blasts + promyelocytes in peripheral blood or bone marrow; ≥20% basophils in
peripheral blood or bone marrow; platelet count <100x109/L unrelated to therapy; or
clonal evolution.

- The patient has either failed, demonstrated intolerance, or a combination of prior
failure and intolerance, to prior treatments with at least 2 tyrosine kinase
inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a
response) or secondary resistance (loss of response).

- TKI treatment failure will be defined as 1 of the following:

- no CHR by 12 weeks (whether lost or never achieved)

- no partial cytogenetic response by 24 weeks (ie, 1 to 35% Ph-positive) (whether
lost or never achieved) no major cytogenetic response by 52 weeks (ie, ≤35%
Ph-positive) (whether lost or never achieved)

- progressive leukocytosis, defined as increasing white blood cell (WBC) count on
at least 2 consecutive evaluations, at least 2 weeks apart and doubling from the
nadir to ≥20000/μL or absolute increase in WBC by ≥50000/μL above the
post-treatment nadir

- Intolerance to TKI therapy will be defined as 1 of the following:

- grade 3 to 4 nonhematologic toxicity that does not resolve with adequate
intervention

- grade 4 hematologic toxicity lasting more than 7 days, or a documented inability
to sustain the TKI therapy because of recurrent grade 3 or 4 hematologic toxicity
with re-initiation of the same therapy

- any grade 2 or greater toxicity that is unacceptable to the patient

- Patients must have completed all previous anticancer therapy for at least 2 weeks
prior to the first planned dose of omacetaxine, except as noted below, and must have
fully recovered from side effects of a previous therapy.

- In patients with rapidly proliferating disease, hydroxyurea may be administered before
study entry, if clinically indicated, to control disease. In such cases, complete
hematologic response (CHR) must be sustained for at least 4 weeks for accelerated CML,
and at least 8 weeks for chronic phase CML, following the discontinuation of
hydroxyurea, to be considered as a CHR.

- Patients may receive anagrelide for up to 28 days (in countries where the product is
registered). Leukapheresis is allowed up to 24 hours prior to the first treatment
cycle with omacetaxine.

- Patients must have adequate hepatic and renal function as evidenced by bilirubin 2.0
times the upper limit of the normal range (ULN) or lower, alanine aminotransferase
(ALT) and asparate aminotransferase (AST) 3 times the ULN or lower, serum creatinine
1.5 times the ULN or lower. Patients with nonclinically significant elevations of
bilirubin up to 5.0 g/dL (85500 μmol/L) due to known or suspected Gilbert's disease
are eligible; this must be documented on the medical history page of the case report
form (CRF).

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 2

- Patients are men or women at least 18 years of age.

- Patients must be able and willing to provide written informed consent prior to any
study related procedure.

- The patient must take precautions to not become pregnant or produce offspring. Women
must be of non-childbearing potential (surgically sterile or postmenopausal for at
least 12 months, confirmed by follicle-stimulating hormone [FSH] >40 IU/L) or agree to
use a medically accepted method of contraception for the duration of the study and 90
days after treatment. Men must be surgically sterile or agree to use a medically
accepted method of contraception for the duration of the study and 90 days after
treatment. Acceptable methods of contraception include abstinence, barrier method with
spermicide (excluding cervical cap and sponge), intrauterine device (IUD), or
steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction
with a barrier method.

- Other criteria may apply, please contact the investigator for additional
information

Exclusion Criteria:

- The patient has New York Heart Association (NYHA) class III or IV heart disease,
active ischemia, or any other uncontrolled cardiac condition such as angina pectoris,
clinically significant cardiac arrhythmia requiring therapy, uncontrolled
hypertension, or congestive heart failure.

- The patient has had a myocardial infarction in the previous 12 weeks. (Prior to study
entry, electrocardiogram [ECG] abnormalities at screening must be documented by the
investigator as not medically relevant.)

- The patient has received radiotherapy within 30 days prior to the start of study drug,
or has not recovered from the acute toxicities associated with prior approved
therapies including investigational drugs.

- The patient has another concurrent illness that would preclude study conduct and
assessment, including, but not limited to, another active malignancy (excluding
squamous or basal cell skin cancer and in situ cervical cancer), uncontrolled medical
conditions, uncontrolled and active infection (considered opportunistic, life
threatening, or clinically significant), uncontrolled risk of bleeding, or
uncontrolled diabetes mellitus.

- The patient underwent autologous or allogeneic stem cell transplant within 60 days
prior to receiving the first dose of omacetaxine and has any evidence of ongoing graft
versus host disease (GVHD), or GVHD requiring immunosuppressive therapy.

- The patient has a human leukocyte antigen (HLA)-matched donor and is eligible for
allogeneic transplantation for CML treatment.

- The patient has known positive human immunodeficiency virus (HIV) or known active
human t-cell lymphotropic virus (HTLV) I/II disease, whether on treatment or not.

- The patient has known active hepatitis B or C. The determination of active hepatitis B
or C is left to the investigator.

- The patient has lymphoid Ph+ blast crisis or blast phase CML.

- The patient participated in another clinical investigation within 30 days of
enrollment or is receiving another investigational agent.

- The patient received omacetaxine or has a history of hypersensitivity.

- Other criteria may apply, please contact the investigator for additional
information