Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older

Prior treatment

• 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 DCIS or 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

Other illness

• Patients with HIV, Hepatitis B, or Hepatitis C
• Unable to tolerate gastrointestinal prophylaxis therapy with sucralfate while on pre-phase and remission induction therapy. Or severe pre-existing GI disorder that requires PPI or H2 receptor antagonist therapy be uninterrupted

Lab values

• Serum creatinine \> 1.5x 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 \> 2x ULN; AST/ALT \> 10x ULN, unless related to ALL liver infiltration.

Other

• 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
• Pregnant women or women who are breast-feeding
• Pre-treatment QTcF \> 480 msecs

• Patient able to give informed consent.
• Patients \>/= 18 years with the following disease will be eligible
  • Newly diagnosed Ph+ ALL, previously untreated, except for the below allowances
  • Previously received HpyerCVAD cycle 1A+/- cycle 1B
  • Previously received Induction Phase 1 +/- Induction Phase II of BFM-modeled (Pediatric of Pediatric-Inspired) ALL regimen
  • Previously received other representative (modified from HyperCVAD, BFM, or AML-like) ALL induction course, including ABL 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 predited to be resistant to dasatibin (e.g. L248R, L248V, Q252H, E255K, V299L, T315A, T315I, F317C, F317L, F317S, F317V)
  • Relapsed or refractory Ph-like ALL without prior exposure to dasatibin and with mutations or rearrangements of genes conferring sensitivity to dasatibin (ABL, CSF1R, PDGFRB) or ruxolitinib (CRLF2, JAK3, EPOR, TSLP)
  • Newly diagnosed or relapsed CML in lymphoid blast crisis
• Confirmation of Philadelphia chromosome positivity by cytogenetics (karyotype/FISH) and/or molecular tests (BCR-ABL1 transcripts)
• Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself
• 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