Download Inclusion criteria

EnestPath CAMN107AIC05
Inclusion criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Male or female patients, aged ≥ 18 years;
2. ECOG performance status of 0-2;
3. Documented confirmed diagnosis of chronic phase Ph+ and/or BCR-ABL+ CML.
Documented chronic phase CML must meet all the following criteria:
• < 15% blasts in peripheral blood and bone marrow
• < 30% blasts plus promyelocytes in peripheral blood and bone marrow
• < 20% basophils in the peripheral blood
• ≥ 100 x 109/L (≥ 100,000/mm3) platelets
4. Previous first-line treatment with imatinib for a minimum of 2 calendar years;
5. Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR;
6. Patient in CCyR; [A patient with MMR is considered in CCyR. Therefore cytogenetic
response assessment has to be done if a patient has less than MMR in the local lab
result or in the blood sample that was sent to EUTOS standardized lab at screening
visit (patient will be considered screening failure if not in CCyR)]
7. Adequate end organ function as defined by:
• Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab).
Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert’s disease)
grade < 3;
• SGOT (AST) and SGPT (ALT) ≤ 3 x ULN;
• Serum amylase and lipase ≤ 2 x ULN;
• Alkaline phosphatase ≤ 2.5 x ULN;
• Serum creatinine < 1.5 x ULN;
8. Patients must have the following electrolyte values within normal limits or corrected to
within normal limits with supplements prior to the first dose of study medication:
• Potassium
• Magnesium
• Total calcium (corrected for serum albumin)
9. Patients must have normal marrow function as defined below:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• with exception of people of North African descent for whom the threshold for
absolute neutrophil count will be ≥1.0 x 109/L due to an increase in the marginal
pool of neutrophils.
• Hemoglobin ≥ 9.0 g/dL
• Platelets ≥ 100 x 109/L
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests
and other study procedures;
11. Written informed consent must be obtained prior to any screening procedures.
EnestPath CAMN107AIC05
Exclusion criteria
Patients eligible for this study must not meet any of the following criteria:
1. Achievement of ≥MR4.0 at study entry;
2. Contraindication to excipients in study medication;
3. Previous treatment with BCR-ABL inhibitors other than imatinib;
4. Patients with any history of detectable atypical BCR-ABL transcripts or patients with
detectable atypical BCR-ABL transcripts at screening;
5. Previous anticancer agents for CML (including Interferon) other than imatinib except for
cytoreduction after CML diagnosis;
6. Patients who are known to be in the chronic phase of CML for the second time after
previous progression to AP/BP;
7. Poorly controlled diabetes mellitus (defined as HbA1c >8%);
8. Impaired cardiac function including any one of the following:
• LVEF < 45% or below the institutional lower limit of the normal range (whichever is
higher)
• Inability to determine the QT interval on ECG
• Complete left bundle branch block
• Right bundle branch block plus left anterior or posterior hemiblock
• Use of a ventricular-paced pacemaker
• Congenital long QT syndrome or a known family history of long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (< 50 beats per minute)
• QTc > 450 msec on the average of three serial screening ECGs (using the QTcF
formula). If QTcF > 450 msec and electrolytes are not within normal ranges,
electrolytes should be corrected and the patient re-tested
• History or clinical signs of myocardial infarction within 12 months of study entry
• History of unstable angina within 12 months of study entry
• Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled
hypertension, unstable angina pectoris)
9. Severe and/or uncontrolled concurrent medical disease that in the opinion of the
investigator could cause unacceptable safety risks or compromise compliance with the
protocol (e.g. uncontrolled diabetes, uncontrolled infection, history of peripheral arterial
occlusive disease);
10. History of acute pancreatitis within 12 months of study entry, or a past medical history of
chronic pancreatitis;
11. Known presence of significant congenital or acquired bleeding disorder unrelated to
cancer;
12. History of other active solid and/or hematologic malignancies within the 5 years prior to
study entry with the exception of previous or concomitant basal cell skin cancer and
previous carcinoma in situ treated curatively;
EnestPath CAMN107AIC05
13. Patients who have not recovered from prior surgery;
14. Treatment with other investigational agents (defined as not used in accordance with the
approved indication) within 4 weeks of Day 1;
15. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which
cannot be either discontinued or switched to a different medication prior to starting study
drug;
16. Patients actively receiving therapy with herbal medicines that are strong CYP3A4
inhibitors and/or inducers which cannot be either discontinued or switched to a different
medication prior to starting study drug. These herbal medications may include Echinacea,
(including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John’s
Wort, and Ginkgo;
17. Patients who are currently receiving treatment with any medications that have the
potential to prolong the QT interval and for which the treatment cannot be either safely
discontinued or switched to a different medication prior to starting study drug (see
http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm for a list of agents that
prolong QT interval);
18. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the
absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome, small bowel resection, or gastric bypass surgery);
19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive hCG
laboratory test;
20. Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using effective methods of contraception during
dosing of study treatment. Effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception;
• Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment;
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• Use of oral, injected or implanted hormonal methods of contraception or other forms
of hormonal contraception that have comparable efficacy (failure rate <1%), for
example hormone vaginal ring or transdermal hormone contraception. In case of use
of oral contraception women should have been stable on the same pill for a minimum
of 3 months before taking study treatment;
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
EnestPath CAMN107AIC05
oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks prior to
enrolling. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow-up hormone level assessment is she considered to
be not of childbearing potential;
21. Patients not able to understand and to comply with study instructions and requirements;
22. Refusal to give informed consent.