| Eligibility |
Inclusion Criteria:
1. study population
a) documented acute myeloid leukemia according to World Health Organization(WHO)
criteria(excluding acute promyelocytic leukemia), with Fms-like Tyrosine Kinase 3
(FLT3) gene mutation,refractory/relapsed after common or enhanced chemotherapy c)
Recovered from toxicity of previous treatment d) Eastern Cooperative Oncology Group
(ECOG) performance status of 0-1 e) Life expectation = 12 weeks
2. Subjects must have adequate organ function and meeting all of the following laboratory
review before enrollment a)blood routine examination: WBC=2000/mm3 b)liver function:
Alanine aminotransferase (ALT) and Aspartate transaminase (AST) =2.5×upper limit of
normal(ULN); serum bilirubin = 1.5 × ULN c)renal function: Serum creatinine = 1.5×ULN,
or the creatinine clearance (CrCl)= 60 mL / min calculated by the Cockcroft-Gault
formula d) electrolyte: serum potassium=3.0mmol/L; serum calcium=2.0 mmol/L e)
abnormal serum amylase without symptom=1.5 × ULN; serum Lipase =1.5× ULN f)
coagulation function:fibrinogen=1.0g/L; activated partial thromboplastin time(
APTT)?ULN+10s; prothrombin time(PT)=ULN+3s g) no obvious organ dysfunction 3)subjects
must volunteer to provide evidence of effective diagnosis prior to entry or to accept
bone marrow puncture or biopsy for diagnosis, and accept bone marrow puncture or
biopsy after treatment to evaluate the efficacy 4) Sign the informed consent
Exclusion Criteria:
Subject meeting any of the following criteria will be excluded.
1. treatment history
1. chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior
to administration;
2. nitrosourea and mitomycin chemotherapy within 6 weeks prior to the
administration;
3. have taken live vaccines within 4 weeks prior to /or concurrent with the
administration;
4. received FLT3 or Axl inhibitors within 6 weeks prior to the administration;
5. have received a trial investigational product, or participated in other clinical
trials within 4 weeks prior to administration
2. disease history and surgery history
a) documented promyelocytic leukemia (t (15; 17) (q22; q11) and / or promyelocytic
leukemia(PML)/retinoic acid receptor alpha (RARa) positivity found in the chromosome,
variant acute promyelocytic leukemia) b) with myeloid sarcoma or invasion of central
nervous system; c) high blood pressure and not well controlled by drug (blood pressure
= 140/90 mmHg). Note: Blood pressure before the first administration (mean blood
pressure of two measures that 24 hours interval or above ) should be controlled within
140/90 mmHg.
d) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) <50%; e)
NCI CTCAE 4.03 = 2 grade of arrhythmia, or corrected QT interval(QTc )> 450 ms ;
patients with a history of torsion or congenital QT prolonged syndrome; f) any of the
illness bellowed within 12 months prior to administration: myocardial infarction,
severe or unstable angina, coronary artery bypass graft or peripheral artery bypass
surgery, congestive heart failure, cerebrovascular events (including Transient
ischemic attack); g) multiple factors that affect oral medication (eg, can not
swallow, chronic diarrhea and intestinal obstruction, etc.); h)obvious tendency of
gastrointestinal bleeding, including the following cases: local active ulcer lesion,
and fecal occult blood test(=++); melena or hematemesis within 2 months;
gastrointestinal bleeding may occurs considered by investigator.
i)history of immunodeficiency, other acquired or congenital immunodeficiency,history
of organ transplantation; j) previous thyroid dysfunction,thyroid function can not be
maintained at the normal range even have drug taken.
k)Human immunodeficiency virus(HIV) positivity l) Hepatitis B surface antigen
(HBsAg)positivity, and in the active phase(hepatitis B nucleic acid quantity= 1.00 ×
103copies / ml); m) Hepatitis C antibody(Anti-HCV) positivity and in the active phase
(hepatitis C nucleic acid quantity =1.00 × 102copies / ml) n) severe retinopathy or
exfoliation judged by the Investigator; o) severe electrolyte imbalance judged by the
investigator; p) active infectious disease judged by the investigator; q) other acute
or chronic medical or psychological illnesses that are not suitable for clinical
trials considered by the investigator or sponsor;
3. Pregnant or lactating women or female and male with fertility plan. 4)the therapy
and/or drug forbidden
1. taking anticoagulant or vitamin K antagonist such as warfarin, heparin or other
similar drugs;
2. taking other anti-leukemia drugs at the same time, including traditional Chinese
medicine (some Chinese medicine can not be used listed in Annex 4);
3. taking drugs that will prolong QT interval(including Ia and III antiarrhythmic
drugs);
4. patients who need oxygen therapy every day;
5. long-term use of corticosteroids (local inhalation excluded);
5)others
a) history of Psychotropic drugs abuse and can not drop or the mentally disordered; b) be
used to drink grapefruit juice or too much tea, coffee and / or caffeine-containing drink,
can not stop during the trial(including Cycle 1 and subsequent treatment period) c) in the
vegistrator's judgment, there is a serious accompany disease that jeopardizes patient's
safety or interfere with the completion of the study.
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