Ruxolitinib Phosphate, Dasatinib, and Dexamethasone in Treating Patients with Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

Inclusion Criteria

• Patient able to give informed consent
• Newly diagnosed Philadelphia chromosome-positive (Ph+) ALL, previously untreated, except for the below allowances: * Previously received hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (HyperCVAD) cycle 1A +/- cycle 1B * Previously received induction phase I +/- induction phase II of Berlin-Frankfurt-Munster (BFM)-modeled (pediatric or pediatric-inspired) ALL regimen * Previously received other representative (modified from HyperCVAD, BFM, or AML-like) ALL induction course, including ABL tyrosine-kinase inhibitor (TKI) plus corticosteroid * If the patient has received any of the above prior therapy, they may be enrolled, regardless of remission status
• Relapsed Ph+ ALL, with no prior exposure to dasatinib and without known ABL kinase mutations predicted to be resistant to dasatinib (e.g. L248R, L248V, Q252H, E255K, V299L, T315A, T315I, F317C, F317I, F317L, F317S, F317V)
• Relapsed or refractory Ph-like ALL without prior exposure to dasatinib and with mutations or rearrangements of genes conferring sensitivity to dasatinib (ABL, CSF1R, PDGFRB) or ruxolitinib (CRLF2, JAK3, EPOR, TSLP)
• Newly diagnosed or relapsed chronic myelogenous leukemia (CML) in lymphoid blast crisis
• Confirmation of Philadelphia chromosome positivity by cytogenetics (karyotype/fluorescence in situ hybridization [FISH]) and/or molecular tests (BCR-ABL1 transcripts)
• Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and for at least 4 months following treatment on study

Exclusion Criteria

• Ph-negative ALL
• Patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis
• Mature B-cell (Burkitt’s) ALL
• Serum creatinine > 1.5 x upper limit of normal (ULN) and calculated creatinine clearance, based on a 24-hour urine collection, < 30 mL/min--unless related to ALL/tumor lysis syndrome and able to be corrected
• Direct bilirubin > 2 x ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 10 x ULN, unless related to ALL liver infiltration
• Pregnant women or women who are breast-feeding
• Patients with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Pre-treatment Fridericia's correction formula (QTcF) > 480 msecs
• A "washout" period of at least 14 days from last previous cytotoxic chemotherapy will be required prior to starting treatment on this protocol; no “washout” period will be required for previous bcr-abl TKI therapy given with the aforementioned previous chemotherapy cycles; hydroxyurea and corticosteroids may be given as bridge therapy up until 24 hours prior to initiating protocol treatment
• Active malignancy requiring treatment other than ALL within two years prior to start of treatment, with the exception of basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, localized prostate cancer, or ductal breast carcinoma in situ (DCIS) or lobular breast carcinoma in situ (LCIS) of the breast
• Active, uncontrolled infection, any other concurrent disease, or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
• Unable to tolerate anti-viral and anti-Pneumocystis jirovecii prophylaxis while on pre-phase and remission induction therapy
• Unable to tolerate gastrointestinal prophylaxis therapy with sucralfate while on pre-phase and remission induction therapy; or severe pre-existing gastrointestinal (GI) disorder that requires peptidylprolyl isomerase (PPI) or histamine H2 (H2) receptor antagonist therapy be uninterrupted