Clinical trial NCT01383447 (phase 1/phase 2, status: terminated)
Conditions: philadelphia chromosome positive adult precursor acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia
ICD codes: C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53
Drugs: entinostat, imatinib mesylate
SMILES: NC1=CC=CC=C1NC(=O)C1=CC=C(CNC(=O)OCC2=CN=CC=C2)C=C1, CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1
Reason stopped: 
    this study was halted prematurely by the nci for low accrual.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed BCR-ABL1 associated (Ph+) acute
             lymphoblastic leukemia (ALL) with primary refractory or relapsed disease;
             demonstration of BCR-ABL1 in leukemia cells by one or more of the following is
             required: t(9;22)(q34;q11.2) cytogenetics; FISH for BCR-ABL1 fusion; RT-PCR for
             BCR-ABL1 fusion

          -  Prior treatment with tyrosine kinase inhibitors (including imatinib, nilotinib and/or
             dasatinib) is allowed, although patients must be off any tyrosine kinase inhibitor for
             a minimum of 72 hours prior to beginning protocol therapy

          -  ECOG performance status of 0, 1 or 2

          -  Total WBC =< 150,000 with no evidence for ongoing or impending leukostasis

          -  Total bilirubin =< 2.0 mg/dL unless elevated due to Gilbert's, hemolysis or leukemic
             infiltration

          -  Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 × upper limit of normal
             (ULN) unless due to leukemic infiltration

          -  Serum creatinine =< 2.0 mg/dL or creatinine clearance > 50 ml/min

          -  Left ventricular ejection fraction (LVEF) >= 45% as measured by echocardiogram (ECHO)
             or MUGA

          -  Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic,
             are eligible provided that they are > 4 weeks from stem cell infusion, have no active
             GVHD, and meet other eligibility criteria

          -  Patients who fail primary induction therapy or relapse after achieving complete
             remission (CR) are eligible if they are > 3 weeks off cytotoxic chemotherapy and > 2
             weeks off radiation therapy; patients must be off biologic therapies including
             hematopoietic growth factors > 1 week; if using hydroxyurea (HU), steroids, or other
             non-cytotoxics for blast count control, patient must be off for > 24 hrs before
             starting protocol therapy; patients must have recovered from all acute toxicities from
             any previous therapy

          -  Female patients of childbearing age must have negative pregnancy test; women of
             child-bearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation; should a woman become pregnant or suspect she is pregnant
             while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents

          -  Active CNS leukemia; patients with known previous CNS leukemia may continue to receive
             intrathecal therapy with ara-C, methotrexate, and/or thiotepa plus steroids as
             prophylaxis against reactivation of previous CNS disease

          -  Patients may not have received previous treatment with entinostat or other HDAC
             inhibitors

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to entinostat or other agents used in study

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             untreated infection, symptomatic congestive heart failure, unstable angina pectoris,
             unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with entinostat

          -  HIV-positive patients on combination antiretroviral therapy are ineligible