The purpose of this study is to test the safety of a new combination of three oral drugs in
Ph+ ALL. These drugs are dexamethasone, dasatinib, and ruxolitinib. All three drugs have
been studied before in humans.
This is a phase I study in which ruxolitinib dose will start low for the first patient
together with dexamethasone plus dasatinib. If this dose does not cause a bad side effect,
the ruxolitinib dose will slowly be made higher as new patients take part in the study. This
will help the investigators find the right dose of ruxolitinib to give together with
dexamethasone and dasatinib that will be used in future studies
Minimum age: 40 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- 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
- Acceptable end-organ function, except for documented exclusions for organ function
compromise due to ALL itself
- Aged 40 years and older
- 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
- 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