Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia
Condition: Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute
Intervention: Cytarabine; CHK1 Inhibitor SCH 900776; Laboratory Biomarker Analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Cytarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well cytarabine with or without SCH 900776 works
      in treating adult patients with relapsed acute myeloid leukemia. Drugs used in chemotherapy,
      such as cytarabine, work in different ways to stop the growth of cancer cells, either by
      killing the cells or stopping them from dividing. SCH 900776 may stop the growth of cancer
      cells by blocking some of the enzymes needed for cell growth. It is not yet known whether
      cytarabine is more effective with or without SCH 900776 in treating acute myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults with the established, pathologically confirmed diagnosis of relapsed AML

          -  AML that has relapsed at least once or is primary induction failure

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Patients must be able to give informed consent

          -  Female patients of childbearing age must have negative pregnancy test

          -  Serum creatinine =< 2.0 mg/dl

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x upper limit
             normal (ULN), unless due to Gilbert's, hemolysis or leukemic infiltration

          -  Alkaline phosphatase =< 5 x ULN, unless due to Gilbert's, hemolysis or leukemic
             infiltration

          -  Bilirubin =< 2.0 mg/dl, unless due to Gilbert's, hemolysis or leukemic infiltration

          -  Left ventricular ejection fraction >= 45% by multi gated acquisition scan (MUGA) or
             echocardiogram

          -  Baseline Fridericia corrected QT (QTcF) < 480 msec

          -  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
             30 days after study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  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
             graft-vs-host disease (GVHD), and meet other eligibility criteria

          -  Patients who fail primary induction therapy or relapse after achieving complete
             remission (CR) are eligible if they have undergone no more than 2 prior cytotoxic
             regimens (a regimen is described as a distinctive planned collection of agent[s]
             and/or modalities to be utilized together during a cycle or course of therapy; i.e.,
             induction+consolidation with or without stem cell transplant [SCT]), >= 2 weeks off
             cytotoxic chemotherapy, and >= 2 weeks off radiation therapy; patients must be off
             biologic therapies including hematopoietic growth factors >= 2 weeks; if using
             hydroxyurea (HU), steroids, imatinib or other tyrosine kinase inhibitors (TKIs),
             interferon, or other non-cytotoxics for blast count control, patient must be off for
             >= 24 hours (hrs) before starting MK-8776

          -  Fluvoxamine and ciprofloxacin must be stopped 7 days prior to day 1 of therapy, and be
             excluded during administration of study therapy; if the subject is using any of the
             other drugs that are cytochrome P4501A2 (CYP1A2) or P-glycoprotein (PgP) inhibitors,
             substitution should be considered and administration of these drugs should be avoided
             on the days of administration of MK-8776; in addition, smoking should be avoided and
             cytochrome P450 3A4 (CYP3A4) substrates with a narrow therapeutic index should be
             avoided: alfentanil, astemizole, cisapride, cyclosporine, diergotamine, ergotamine,
             fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine

        Exclusion Criteria:

          -  Any previous treatment with MK-8776

          -  Considered refractory or treatment failure to most recent treatment regimen, unless
             primary refractory

          -  Concomitant chemotherapy, radiation therapy, or immunotherapy

          -  Hyperleukocytosis with >= 50,000 blasts/uL (if using HU, steroids, tyrosine kinase/src
             inhibitors (including fms-related tyrosine kinase 3 [FLT3] inhibitors), arsenic,
             interferon or leukapheresis for blast count control, patient must be off those agents
             for 24 hours prior to beginning ara-C +/- MK-8776)

          -  Acute progranulocytic leukemia (APL, M3)

          -  Active disseminated intravascular coagulation (DIC)

          -  Active central nervous system (CNS) leukemia

          -  Active, uncontrolled infection; patients with infection under active treatment and
             controlled with antibiotics are eligible

          -  Presence of other life-threatening illness

          -  Patients with mental deficits and/or psychiatric history that preclude them from
             giving informed consent or from following protocol

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with MK-8776

          -  History of Fridericia corrected QT (QTcF) prolongation greater than grade 1 or 480
             msec

          -  Subjects with the following cardiac risk factors must be excluded: transmural
             myocardial infarction (MI) within prior 6 months, severe/unstable angina pectoris,
             coronary/peripheral artery bypass graft, cerebrovascular accident or transient
             ischemic attack (TIA) or seizure disorder within 6 months prior to study drug
             administration

          -  Subjects with history of risk factors for torsades de pointes: clinical history of
             heart failure (New York Heart Association [NYHA] class III or IV), hypo- or
             hyper-kalemia or hypomagnesemia (supplementation to bring levels within normal limits
             prior to administration of MK-8776 is acceptable) or family history of Long QT
             Syndrome

          -  Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy
             or who have a prior history of acquired immunodeficiency syndrome (AIDS) indicator
             conditions, other than history of lymphoma more than 3 years remote