Key Inclusion Criteria
- Patients ≥ 18 years of age.
- Baseline ECOG Performance Status ≤ 2, and patient is a candidate for intensive
chemotherapy.
- Newly diagnosed Ph+ ALL.
- Written informed consent prior to any screening procedures. Permitted exceptions are
that the diagnostic marrow exam/peripheral blood/nodal biopsy tests confirming Ph+
B-Cell ALL, as well as pre-induction cardiac workup (EKG/TTE/MUGA), may be performed
prior to the patient providing written informed consent if these tests are within 14
days of enrollment.
- Patient able to give informed consent.
- B-cell Acute Lymphoblastic Leukemia with BCR-ABL1, i.e., Philadelphia
chromosome-positive (Ph+) ALL.
- B-Cell lineage determined by standard flow cytometry/IHC
- 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 and up until
48 hours after starting trial therapy:
- Corticosteroids
- Hydroxyurea
- Leukapheresis
Key Exclusion Criteria
- Any of the following subtypes of ALL:
- Ph-negative B-Cell ALL.
- T-Cell ALL.
- Relapsed Ph+ ALL.
- Lymphoid blast crisis of chronic myeloid leukemia (CML).
- Mature B-Cell (Burkitt's) ALL.
- Clinical signs of CNS disease.
- Active ALL in CNS or testes.
- Estimated Glomerular Filtration Rate (eGFR) by MDRD formula and calculated creatinine
clearance (CrCl), based on a 24-hour urine collection, < 30 mL/min-unless related to
ALL/tumor lysis syndrome and able to be corrected.
- Total Bilirubin > 2x ULN; AST/ALT > 10x ULN, unless related to ALL liver infiltration.
- Patients with known history of HIV, Hepatitis B, or Hepatitis C.
- Pre-treatment QTcF > 480 msecs.
- Left Ventricular Ejection Fraction < 45%. If an initial TTE demonstrates LVEF < 45%, a
confirmatory MUGA should be performed to confirm LVEF is < 45% prior to excluding the
patient. Both a TTE and a MUGA with LVEF < 45% are needed to exclude a patient. Either
a TTE or MUGA alone, if LVEF is ≥ 45%, is sufficient to include a patient.
- Have significant or active cardiovascular disease, specifically including but not
restricted to:
- Known prior type 1 (thrombotic) myocardial infarction (type 2 myocardial
infarction/demand ischemia is not necessarily excluded).
- History of clinically significant atrial arrhythmia or any ventricular
arrhythmia.
- Unstable angina within the last 12 months.
- Congestive heart failure within the last 12 months.
- Currently uncontrolled hypertension (≥ Grade 3; or systolic blood pressure ≥ 160
mm Hg and/or diastolic blood pressure ≥ 100 mm Hg).
- Acute pancreatitis within the last year or a history of chronic pancreatitis.
- Have malabsorption syndrome or other gastrointestinal illness that could affect the
absorption of orally administered chemotherapy.
- Ongoing uncontrolled severe nausea or vomiting.
- History of a significant bleeding disorder unrelated to ALL, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
VIII antibodies).
- Taking any medications or herbal supplements that are known to be strong inhibitors or
inducers of CYP3A4 within at least 7 days or 5 half-lives (whichever is longer) before
the first dose of study chemotherapy on day 1 of Remission Induction Phase I (RIP1).
- 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,
colon polyp, 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.
- Pregnant women or women who are breast-feeding
- Men and women of childbearing potential must be willing to practice an effective
method of birth control during treatment and up until 30 days following the end of
trial therapy.
