- Patient able to give informed consent.
- Precursor B-cell acute lymphoblastic leukemia Philadelphia chromosome-positive (Ph+) patients.
- Precursor B-cell lineage determined by standard flow cytometry.
- Ph+ by cytogenetics (karyotype/FISH) and/or molecular (BCR-ABL1 transcripts)
- Determined in CLIA-certified laboratory
- Previously untreated, except for below allowances in a recent diagnosis:
- Previously received HyperCVAD cycle 1A +/- cycle 1B.
- Previously received Induction Phase I +/- Induction Phase II of BFM-modeled (Pediatric or Pediatric-Inspired) ALL regimen
- Previously received other representative (modified from HyperCVAD, BFM, or AML- like) ALL induction course
- Including bcr-abl TKI plus corticosteroid
- Patients with relapsed Ph+ ALL, including both molecular and morphologic relapse.
- Patients aged > 18 with Ph-like ALL, either newly diagnosed, minimally treated, or relapsed. Ph-like ALL with mutations or rearrangements known to respond to either dasatinib or ruxolitinib will be eligible, and include fusions involving ABL1, ABL2, CSF1R and PDGFRB (for dasatinib) and EPOR, JAK2 and CRLF2 (for ruxolitinib).
- Patients with CML in lymphoid blast crisis, either untreated or relapsed.
- Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself
- Aged 40 years and older. Patients with newly diagnosed or minimally treated ALL younger than 40 are allowed if they are unfit to receive conventional chemotherapy.
- 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
- Ph-negative ALL
- Relapsed Ph+ ALL or patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis
- Lymphoid blast crisis of chronic myelogenous leukemia (CML)
- Mature B-cell (Burkitt's) ALL
- Clinical signs of CNS disease
- Active ALL in CNS or testes
- 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.
- Pregnant women or women who are breast-feeding
- Patients with HIV, Hepatitis B, or Hepatitis C
- Pre-treatment QTcF > 480 msecs
- 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, 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
- 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
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||40 Years|