HEM-iSMART-B: Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

Inclusion Criteria: 1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion 2. Performance status: Karnofsky performance status (for patients \>12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 50% (Appendix I). 3. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines. 4. For all oral medications patients must be able to comfortably swallow capsules (except for those for which an oral solution is available or dissolving of tablets is allowed based on investigator brochure (IB); nasogastric or gastrostomy feeding tube administration is allowed only if indicated). 5. Patients must have had advanced molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with advanced molecular profiling at diagnosis may be allowed to be included after discussion with the sponsor. 6. Patients whose tumor present the following alterations: NUP214-ABL1 fusion or other ABL1 fusion, activating the kinase domain, or ABL1 amplification, or PDGFRβ-fusion with various fusion partners including but not limited to: AGGF1, DOCK2, SATB1, ETV6 and/or Patients showing a very deep ex-vivo dasatinib IC50 below 10 nM (Only data generated in centralized laboratory, where a robust DRP platform has been established with a reference cohort in place, will be considered) 7. Adequate organ function: * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) : * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL/min/1.73 m2. * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome). * Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility. * CARDIAC FUNCTION: * Shortening fraction (SF) \>29% (\>35% for children \< 3 years) and/or left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA. * Absence of QTcF prolongation (QTc prolongation is defined as \>450 msec on baseline ECG, using the Friedericia correction), or other clinically significant ventricular or atrial arrhythmia. Exclusion Criteria: 1. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1. 2. Sexually active participants not willing to use highly effective contraceptive method (pearl index \<1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy. 3. Breast feeding. 4. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs. 5. Patients whose tumor present known mutationts confering resistance to venetoclax (e.g. BCL2 mutations of venetoclax binding-site (Gly101Val mutation, Phe104Leu/Cys mutations). 6. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide when applicable, intrathecal agents) and corticoids. 7. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection. a. Additional specifications for SARS-CoV-2 (COVID-19): i. Patients with a recent positive test for SARS-CoV-2 (COVID-19) and no follow-up negative PCR test are not eligible. ii. Patients with recent contact to persons with COVID-19 and persons with signs and symptoms of COVID-19 infection must be tested before enrolling. In case of contact with a COVID-19 positive person, at least 5 days should be observed between last contact and COVID testing. A negative PCR test is required to be eligible. iii. A negative COVID-19 test result is defined as at least 1 negative PCR test at least 24 hours after resolution of clinical symptoms. Resolution of clinical symptoms is defined as resolution of fever without use of antipyretics and improvement in respiratory symptoms (e.g., cough, shortness of breath). iv. Frequency or timing of COVID-19 testing and interval between testing for the above viral clearance criteria may be adjusted to the applicable country and institutional guidelines. 8. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion. 9. Subjects unwilling or unable to comply with the study procedures. 10. Previous treatment with dasatinib and venetoclax in combination (Patients who have previously received any of these two drugs separately can be eligible for this sub-protocol). 11. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7, Appendix III and IV for details. In general, CYP3A4 inhibitors/Pgp inhibitors, moderate or strong inducers of CYP3A4 or drugs inducing QTc changes (prolongation of the QT interval o