A Phase 1 Dose-Escalation Study of SCH 900776 in Combination With Cytarabine in Subjects With Acute Leukemias
- Subject must have a histologically or cytologically confirmed diagnosis of relapsed
and/or refractory acute leukemia, including
- acute myelogenous leukemia, including AML arising from myelodysplasia (MDS) or
myeloproliferative disorder (MPD);
- acute lymphocytic leukemia, including Philadelphia chromosome-positive (Ph+) ALL
(Dose-Escalation Part only);
- chronic myelogenous leukemia (CML) in accelerated phase (AP) or blast crisis
(BC) of either myeloid or lymphoid origin (Dose-Escalation Part only);
- treatment-related high-grade MDS (ie, refractory anemia with excess blasts in
- MPD in transformation [eg, CMMoL-T (5%-19% blasts)].
- Subject must have recurred or progressed following standard therapy or failed
standard therapy, or have disease for which no standard therapy currently exists.
- Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0, 1, or 2.
- Subject must be 18 years or older, of either sex, and of any race.
- Subject (and/or parent/guardian for subjects who otherwise is unable to provide
independent consent) must be willing to give written informed consent and be able to
adhere to dose and visit schedules.
- Female subject of childbearing potential must have a negative pregnancy test within 5
days prior to first dose of cytarabine.
- Female subject of childbearing potential and male subject whose sexual partner is of
childbearing potential must agree to abstain from sexual intercourse or to use an
acceptable method of contraception during the study and for 90 days following the
last dose of protocol therapy. Acceptable methods of contraception include condoms
(male or female) with or without spermicidal agent, diaphragm or cervical cap with
spermicide, medically prescribed intrauterine device (IUD), oral or injectable
hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal
- Subject must have adequate renal function as evidenced by a serum creatinine level
<=1.5 x upper limit of normal (ULN) or a calculated creatinine clearance >=60 mL/min.
- Subject, except one with known Gilbert's Syndrome, must have adequate hepatic
function as evidenced by a serum bilirubin level <=1.5 mg/dL AND serum levels of
aspartate and alanine aminotransferase (AST/ALT) <=5 x the ULN for the reference
- Subject must have adequate cardiac function with a left ventricular ejection fraction
(LVEF) of >=45% (echocardiogram or multiple-gated acquisition [MUGA] scan).
- Subject must be recovered from the effects of any prior surgery, radiotherapy, or
systemic antineoplastic therapy.
- Subject who was refractory to or relapsed after prior allogeneic or autologous stem
cell transplant is eligible.
- Subject must not have known hypersensitivity to SCH 900776 or cytarabine or to any of
their excipients or have received therapy with another CHK1 inhibitor.
- Subject must not have received any medication listed below more recently than the
indicated washout period prior to first dose of protocol therapy and must not
continue to receive treatment that is listed below.
- Subject must not have persistent, unresolved CTCAE v 3.0 >=Grade 2 drug-related
toxicity (except alopecia, erectile impotence, hot flashes, decreased libido,
hematologic toxicity) associated with previous treatment.
- Subject must not have known human immunodeficiency virus (HIV), hepatitis B or
hepatitis C, or have a known history of liver cirrhosis or active alcohol abuse.
- Subject must not be New York Heart Association (NYHA) Class III (has marked
limitation in activity due to symptoms, even during less than ordinary activity [eg,
walking short distances >20-100 m]; is comfortable only at rest) or Class IV (has
severe limitations; experiences symptoms even while at rest; mostly bed bound).
- Subject must not have any other medical or psychiatric condition that, in the opinion
of the investigator, might interfere with the subject's participation in the trial or
interfere with the interpretation of trial results.
- Subject must not have undergone major surgery within 3 weeks prior to first study
drug administration after enrollment.
- Subject must not have known active CNS or leptomeningeal leukemia.
- Subject must not have received radiation therapy within 2 weeks prior to first study
drug administration after enrollment or radiation therapy to >25% of bone marrow.
- Subject must not have received more than 4 prior induction regimens.
- Subject must not have a peripheral blast count >=50,000/mm3.
- Subject must not have active, uncontrolled graft versus host disease (GVHD)
post-allogeneic stem cell transplant.
- Subject must not have had any of the following within 6 months prior to first study
drug administration after enrollment: myocardial infarction, severe/unstable angina
pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart
failure, cerebrovascular accident or transient ischemic attack, or seizure disorder.
- Subject must not have a known bleeding diathesis, eg, hemophilia, or disseminated
- Subject must not have an active, uncontrolled infection.
- Subject must not have a history of cytarabine-related neurotoxicity.
- Subject must not have a baseline QTc interval >470 msec (ie, CTCAE v 3.0 Grade >=2).
- Subject must not currently be a smoker and/or must not be likely to smoke during the
- Female subject must not be breast-feeding, pregnant, or intend to become pregnant.
- Subject must not be participating in any other interventional clinical study.
(Subject participating in another non interventional study may be considered after
discussion with the sponsor).