Phase III Study of Compound Realgar Formula Realgar-Indigo Naturalis Plus Imatinib Versus Placebo Plus Imatinib in Adult Patients With Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
1. Male or female patients, age >= 18 years and <= 75 years.
2. Eastern Cooperative Oncology Group （ECOG） performance status (PS) score 0, 1, or 2.
3. Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of
Philadelphia chromosome positive.(Ph+ CML-CP)
4. Ph+ Chronic myelogenous leukemia in chronic phase patients within the first 12 months
5. Adequate end organ function as defined by:
(1). Alanine transaminase（ALT）, Aspartate transaminase（AST） <=2.5 x upper limit of
(2). Total bilirubin <= 1.5 x ULN. (3).Cr <= 1.5 x ULN. (4). Serum amylase and lipase <=
1.5 x ULN. 6. Signed informed consent.
1. Previously received or be receiving any of the following medical treatment for CML:
1. . Treatment with Busulfan within 1 day prior to study entry.
2. . Treatment with interferon-alpha within 2 days prior to study entry.
3. . Treatment with hydroxyurea within 1 day prior to study entry.
4. . Treatment with homoharringtonine within 14 days prior to study entry.
5. . Treatment with Cytosine arabinoside within 28 days prior to study entry.
6. . Surgery (Including hematopoietic stem cell transplantation therapy)
7. . Treatment with anthracyclines, or etoposide within 21 days prior to study entry.
2. Treatment with any tyrosine kinase inhibitor(s) or arsenic reagent prior to study
entry 3. Patients who are: (a) pregnant, (b) breast feeding, (c) female or male of
childbearing potential unwilling to use contraceptive precautions throughout the trial.
4. Major surgery within 4 weeks prior to randomization or who have not recovered from
5. Patients who have not recovered from toxic reaction of prior similar treatment
evaluated by investigators.
6. Impaired cardiac function including any one of the following:
1. LVEF < 45%.
2. . Complete left bundle branch block.
3. . Use of a ventricular-paced pacemaker.
4. . Congenital long QT syndrome.
5. . History or presence of ventricular, clinically significant atrial tachyarrhythmias
6. . History or presence of clinically significant bradyarrhythmia.(heart rate
persistently less than 50/min)
7. . QTcF > 450 msec for male or 470 msec for female.
8. . History of clinically documented myocardial infarction or unstable angina (during
the last 12 month).
9. .Any other severe heart disease. 7. Patients with active, uncontrolled psychiatric
disorders, without insight and the ability of exact expression.
8. Uncontrolled medical conditions:
1. .Uncontrolled diabetes with fasting blood-glucose >200mg/dl (11.1mmol/L),or with
combined symptoms (nephropathy, peripheral neuropathy).
2. . Uncontrolled hypertension.
3. . Active or uncontrolled infection (persistent fever and worsening of the clinical
symptoms) 9. Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the tested drug (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel
resection, or gastric bypass surgery).
10. History of chronic pancreatitis or history of acute pancreatitis within 1 year of
11. Acute or chronic uncontrolled liver disease or severe renal disease considered
unrelated to CML.
12. Patients actively receiving therapy with strong CYP3A4 inhibitors, strong CYP3A4
inducers or any medications being potential to prolong the QT interval and the treatment
cannot be either discontinued or switched to a different medication prior to starting
13. Treatment with other investigational agents (defined as not used in accordance with
the approved indication) within 4 weeks prior to randomization.
14. Known to be allergic to the study drugs, including crude drug or adjuvant. 15. As
investigators evaluate, the patients do not fit to join the study (such as with severe