Evaluation of ETC-1907206 With Dasatinib in Advanced Haematologic Malignancies

INCLUSION CRITERIA: Each patient (male or female) must meet all of the following criteria to be enrolled in this study: 1. Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements. 2. Age 18 years or older (US sites) or 21 years or older (Singapore site) at Baseline. 3. Bone marrow (BM) cytogenetic analysis with at least 20 metaphase cells, confirmed advanced haematologic malignancies in any of the 4 following disease populations at Screening: * CML-AP, Ph+ * CML-BC, Ph+ * Ph+ ALL * Ph- ALL with relapsed and refractory disease who have exhausted all available therapy (for patients who develop T315I mutation related resistance, the definition requires failure of ponatinib treatment if drug is accessible). 4. Meets definition for one of the following study subgroups: CML-AP: * ≥ 15% and \< 30% blast in peripheral blood or bone marrow, or * ≥ 20% basophils in peripheral blood or bone marrow or * ≥ 30% blasts + promyelocytes in peripheral blood or bone marrow (but \< 30% blasts) or * \< 100 x 10\^9 platelets/L in peripheral blood unrelated to therapy or * Cytogenetic, genetic evidence of clonal evolution and * No extramedullary disease. CML-BC: * ≥ 30% blasts in peripheral blood or bone marrow, or * extramedullary disease other than hepatosplenomegaly. Ph+ ALL: * ≥ 30% blasts in blood or bone marrow and * no prior history of CML. Ph- ALL: * ≥ 10% blasts in bone marrow. 5. ECOG performance status of 0 to 2 at Baseline. 6. Life expectancy of at least 3 months at Baseline. 7. Adequate organ function at Baseline, including the following (noting that repeated tests at Baseline should not be performed unless there are sufficient reasons to assume the patient would meet the inclusion criteria with re testing): 1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN), unless resulting from haemolysis or documented Gilbert syndrome. 2. Transaminases \[aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x ULN\]. \[\< 5 x ULN if liver infiltration with tumour present\] 3. Prothrombin time (PT) \< 1.5 ULN. 4. Calculated creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula). 5. No clinically relevant abnormalities in the urinalysis results. 6. Haematology: * Haemoglobin \> 10 g/dL (transfusion allowed to reach the level) * Neutrophils \> 1,000/µL * Platelets \> 75,000/µL. 7. Pancreatic status: * Lipase ≤ 1.5 x ULN * Amylase ≤ 1.5 x ULN. 8. Capable of taking oral medication and following direction regarding taking study drug (either by himself/herself or by caregiver). 9. Negative serum pregnancy test at Baseline plus a negative urine pregnancy test on Day 1, Cycle 1 prior to treatment (applies to females of childbearing potential only). 10. A minimum of 2 weeks (14 days), or 5 half-lives (whichever is shorter) since last receipt of any anti-cancer therapy (except dasatinib, hydroxyurea, anagrelide or steroids), or 4 weeks from radiation or major surgery to the first administration of the study drug. 11. All non-haematological AEs of any prior anti-cancer therapy, surgery, or radiotherapy have to be resolved to NCI CTCAE Grade ≤ 1 (except alopecia) within 2 weeks prior to starting study drug. 12. Willing to submit the blood samples and bone marrow samples for PK and pharmacodynamic (PD) analyses. CML-AP Ph+, CML-BC Ph+, Ph- ALL, and Ph+ ALL patients with relapsed and refractory disease who have exhausted all available therapy. Subgroup-specific intolerance definition: \[Intolerance to tyrosine kinase inhibitors (TKIs) or other approved treatments for CML-AP, CML-BC and Ph+ ALL; to approved treatments for Ph- ALL\] defined as: * Non-haematologic 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 a dose reduction is not considered in the best interest of the patient if response is already suboptimal) in absence of: major haematologic response (MaHR) for accelerated phase (AP), blast crisis (BC) or Ph+ ALL patients; complete remission (CR) or complete haematological response with partial haematologic recovery of peripheral blood count (CRh) for Ph- ALL. * Haematologic 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 dose recommended by drug manufacturers in the absence of: MaHR for AP, BC or Ph+ ALL patients; CR or CRh for Ph- ALL. NOTE: For dasatinib, non-haematologic and haematologic intolerance is defined as: CTCAE Grade \> 2 requiring discontinuation. EXCLUSION CRITERIA: Patients meeting any of the following criteria will be excluded from the study: 1. Is a male patient with sexual partner(s) of childbearing potential who is unwilling to use a highly effective method of contraception, one of which includes a condom. Sexually active male patients must use a condom during intercourse throughout the study and for 12 weeks after the end of treatment and should not father a child in this period. A condom is required to be used also by vasectomised males in order to prevent potential delivery of the study drug via seminal fluid. Female partners of male patients must be advised to also use one of the following contraception methods: * intrauterine device or intrauterine system; * prior sterilisation; or * total abstinence from male/female intercourse. 2. Is a female patient of childbearing potential, defined as a female physiologically capable of becoming pregnant (including a female whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, and females whose partners have been sterilised by vasectomy or other means), unless they are using a highly effective method for birth control throughout the study and for 12 weeks after the end of treatment. Highly effective methods for birth control include the following: * Total abstinence: This is an acceptable method when this is consistent with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Female sterilisation: The patient has had a surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to taking study drug. In case of an oophorectomy alone, the reproductive status of the patient must have been confirmed by follow-up hormone level assessment. * Male partner sterilisation: The patient has the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. (For female patients on the study, the vasectomised male partner should be the sole partner for that patient.) These patients must also agree to the use an intrauterine device or intrauterine system AND a barrier method of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, or cream, or vaginal suppository. Reliable contraception must be maintained throughout the study and for 12 weeks after study drug discontinuation. * Females considered post-menopausal and not of childbearing potential: The definition applies to females who have had 12 months of natural (spontaneous) amenorrhoea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhoea with serum follicle-stimulating hormone (FSH) levels \> 40 million international units per milliliter (mIU/mL) (for US only: and estradiol \< 20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to starting treatment. In the case of oophorectomy alone, only when the reproductive status of the patient has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential. 3. Is a pregnant or nursing (lactating) female, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 5 mIU/mL). 4. Has dasatinib intolerance (haematologic and non-haematologic). Defined as: CTCAE Grade \>2 5. Has received anti-cancer therapy within 2 weeks or 5 half-lives, whichever is shorter (except for hydroxyurea, steroids, allopurinol, febuxostat, rasburicase, and intravenous hydration), prior to starting study drug or the side effects of such therapy have not resolved to Grade ≤1 within 2 weeks prior to starting study drug. 6. Is receiving concomitant anti-cancer therapy (except for hydroxyurea, steroids, anagrelide, allopurinol, febuxostat, rasburicase, and intravenous hydration during the first week of the study drug\[s\] administration, or corticosteroids when appropriate). 7. Has used other investigational drugs within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug. 8. Has undergone autologous or allogenic stem cell transplantation \< 60 days prior to the first dose of study drug; 9. Has any evidence of on-going graft-versus-host disease (GVHD). 10. Has evidence of another malignancy not in remission or history of such a malignancy within the last 3 years (except for treated basal or squamous cell carcinoma of the skin, or in situ cancer of the cervix). 11. Has central nervous system (CNS) metastases. 12. Has significant bleeding disorder unrelated to the disease. 13. Has a history of long QT syndrome or prolonged QT interval corrected based on Fridericia's method (QTcF) \> 450 ms. 14. Has ECG evidence of complete left bundle branch block, or ventricular pacing. 15. Has abnormalities in the 12-lead ECG that in the opinion of the Investigator increase the risk of participating in the study (e.g., sinus rhythm with PR interval \> 240 ms or second degree or higher atrioventricular (AV) block confirmed by a repeat ECG). 16. Has blood pressure and heart rate (HR) higher than 160/100 mmHg and 100 beats per minute (bpm), respectively, or lower than 80/50 mm Hg and 45 bpm, respectively, confirmed by a repeat assessment. 17. Is receiving treatment with drugs known to be associated with Torsade de Pointes. 18. Has ophthalmic signs or symptoms, such as flashes and colour perception changes. 19. Has evidence of electrolyte imbalance such as hypokalaemia, hypocalcaemia, and hypomagnesaemia of NCI-CTCAE Grade ≥ 2 (NCI CTCAE version 4.03). 20. Has symptomatic chronic heart failure; unstable angina pectoris, cardiac arrhythmia. 21. Has cardiac left ventricular ejection fraction (LVEF) \< 40% (assessed by transthoracic echocardiography). 22. Has a history of myocardial infarction and/or thromboembolism in the past 6 months. 23. Has uncontrolled diabetes mellitus, neurologic or psychiatric condition, an ongoing systemic (including opportunistic) clinically significant infections or any other significant or unstable concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy. 24. Has a known history of human immunodeficiency virus (HIV) sero positivity and/or is receiving combination anti retroviral therapy. 25. Has a history of gastric bypass surgery or with pre-existing gastrointestinal disorders that may interfere with proper absorption of the drug, as per Investigator's judgement. 26. Has history of seizure disorders or CNS leukaemia. 27. Is receiving cytochrome P450 3A4 (CYP3A4) inhibitors within 7 days prior to the first dose of ETC-1907206 or receiving CYP3A4 inducers within 14 days prior to the first dose of ETC-1907206 and dasatinib. 28. Cannot start treatment with dasatinib 140 mg daily, oral. 29. Is unwilling or unable to comply with the protocol