Patients eligible for inclusion in this study have to meet all of the following criteria:

1. Male or female patients with a diagnosis of CML-CP ≥ 18 years of age

2. Patients must meet all of the following laboratory values at the screening visit:

< 15% blasts in peripheral blood and bone marrow

< 30% blasts plus promyelocytes in peripheral blood and bone marrow

< 20% basophils in the peripheral blood

≥ 50 x 109/L (≥ 50,000/mm3) platelets

·Transient prior therapy related thrombocytopenia (< 50,000/mm3 for ≤ 30 days prior

to screening) is acceptable

· No evidence of extramedullary leukemic involvement, with the exception of

hepatosplenomegaly

3. BCR-ABL ratio ≥ 1% IS according to central laboratory at the screening examination

4. Prior treatment with a minimum of 2 prior ATP-binding site TKIs (i.e. imatinib, nilotinib,

dasatinib, radotinib or ponatinib)

5. Failure or intolerance to the last previous TKI therapy at the time of screening (adapted

from the 2013 ELN Guidelines Bacarrani 2013)

· Failure is defined for CML-CP patients (CP at the time of initiation of last therapy) as

follows. Patients must meet at least 1 of the following criteria.

· Three months after the initiation of therapy: No CHR or > 95% Ph+ metaphases

· Six months after the initiation of therapy: BCR-ABL ratio > 10% IS and/or > 65%

Ph+ metaphases

Twelve months after initiation of therapy: BCR-ABL ratio > 10% IS and/or > 35%

Ph+ metaphases

· At any time after the initiation of therapy, loss of CHR, CCyR or PCyR

· At any time after the initiation of therapy, the development of new BCR-ABL

mutations

· At any time after the initiation of therapy, confirmed loss of MMR in 2

consecutive tests, of which one must have a BCR-ABL ratio ≥ 1% IS

· At any time after the initiation of therapy, new clonal chromosome abnormalities

in Ph+ cells: CCA/Ph+

Intolerance is defined as:

· Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy,

or with persistent grade 2 toxicity, unresponsive to optimal management,

including dose adjustments (unless dose reduction is not considered in the best

interest of the patient if response is already suboptimal)

· Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil

count [ANC] or platelets) while on therapy that is recurrent after dose reduction

to the lowest doses recommended by manufacturer

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

7. Adequate end organ function as defined by (as per central laboratory tests):

· Total bilirubin ≤ 1.5 x ULN except for patients with Gilbert’s syndrome who may

only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN

· Aspartate transaminase (AST) ≤ 3.0 x ULN

· Alanine transaminase (ALT) ≤ 3.0 x ULN

· Serum amylase ≤ ULN

· Serum lipase ≤ ULN

· Alkaline phosphatase ≤ 2.5 x ULN

· Creatinine clearance ≥ 50 mL/min as calculated using Cockcroft-Gault formula

8. Patients must avoid consumption of grapefruit, Seville oranges or products containing the

juice of each during the entire study and preferably 7 days before the first dose of study

medications, due to potential CYP3A4 interaction with the study medications. Orange

juice is allowed.

9. Written informed consent obtained prior to any screening procedures.

10. Patients must have the following electrolyte values within normal limits (as per central

laboratory tests) or corrected to be within normal limits with supplements prior to first

dose of study medication:

· Potassium

· Magnesium

· Total calcium (corrected for serum albumin)

Patients eligible for this study must not meet any of the following criteria:

1. Known presence of the T315I or V299L mutation at any time prior to study entry

2. Known second chronic phase of CML after previous progression to AP/BC

3. Previous treatment with a hematopoietic stem-cell transplantation

4. Patient planning to undergo allogeneic hematopoietic stem cell transplantation

5. Cardiac or cardiac repolarization abnormality, including any of the following:

· History within 6 months prior to starting study treatment of myocardial infarction

(MI), angina pectoris, coronary artery bypass graft (CABG)

· Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left

bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II

and third degree AV block)

· QTcF at screening ≥450 ms (male patients), ≥460 ms (female patients)

· Long QT syndrome, family history of idiopathic sudden death or congenital long QT

syndrome, or any of the following:

· Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or

hypomagnesemia, history of cardiac failure, or history of clinically

significant/symptomatic bradycardia

· Concomitant medication(s) with a known risk to prolong the QT interval and/or

known to cause Torsades de Pointes that cannot be discontinued or replaced 7

days prior to starting study drug by safe alternative medication.

· Inability to determine the QTcF interval

6. 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, active or uncontrolled infection, pulmonary

hypertension)

7. History of acute pancreatitis within 1 year of study entry or past medical history of chronic

pancreatitis

8. History of elevation in amylase or lipase (> ULN) within 1 year other than that which may

have occurred with gallstones, trauma, or medical procedures

9. History of acute or chronic liver disease

10. Known presence of significant congenital or acquired bleeding disorder unrelated to

cancer

11. History of other active malignancy within 3 years prior to study entry with the exception

of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated

curatively

12. Known history of Human Immunodeficiency Virus (HIV), chronic Hepatitis B (HBV), or

chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag)

and Hepatitis B core antibody (HBcAb / anti HBc) will be performed at screening

13. 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)

14. Treatment with medications that meet one of the following criteria and that cannot be

discontinued at least one week prior to the start of treatment with study treatment

· Moderate or strong inducers of CYP3A

· Moderate or strong inhibitors of CYP3A and/or P-gp

· Substrates of CYP3A4/5, CYP2C8, or CYP2C9 with narrow therapeutic index

15. Previous treatment with or known/ suspected hypersensitivity to ABL001 or any of its

excipients.

16. Previous treatment with or known/ suspected hypersensitivity to bosutinib or any of its

excipients.

17. Participation in a prior investigational study within 30 days prior to randomization or

within 5 half-lives of the investigational product, whichever is longer

18. Pregnant or nursing (lactating) women

19. Women of child-bearing potential, defined as all women physiologically capable of

becoming pregnant, unless they are using highly effective methods of contraception

during dosing and for 3 days after last dose of ABL001. Highly 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) total 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

· Male sterilization (at least 6 months prior to screening). The vasectomized male

partner should be the sole partner for that subject.

· Use of oral, injected or implanted hormonal methods of contraception or placement of

an intrauterine device (IUD) or intrauterine system (IUS) 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.

20. 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

oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least

six weeks ago. 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

not of child bearing potential.

21. Sexually active males unless they use a condom during intercourse while taking the drug

during treatment and for 3 days after stopping treatment and should not father a child in

this period. A condom is required to be used also by vasectomized men as well as during

intercourse with a male partner in order to prevent delivery of the drug via semen.