A Phase 1 Study of Entinostat an Oral Histone Deacetylase Inhibitor in Pediatric Patients With Recurrent or Refractory Solid Tumors Including CNS Tumors and Lymphoma

Inclusion Criteria
Patients must have a body surface area (BSA) of >= 1.17 m^2 at time of study enrollment
Patients must be able to swallow intact tablets
Patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors or lymphoma, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Patients must have either measurable or evaluable disease
Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients == 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
Lymphoma patients: a waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e. corticosteroid, vincristine, thioguanine[6MP], and/or methotrexate)
>=14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy; additionally, patients must have fully recovered from all acute toxic effects of prior therapy; Note: cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days must have elapsed from the last dose of agent; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade == 14 days must have elapsed from the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days must have elapsed from the last dose of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell infusions (with or without traumatic brain injury [TBI]):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days must have elapsed from infusion and no evidence of graft versus host disease (GVHD)
Autologous stem cell infusion including boost infusion: >= 42 days must have elapsed from infusion
Cellular therapy: >= 42 days must have elapsed from last dose of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
External beam radiation (XRT)/External beam irradiation including protons: >= 14 days must have elapsed after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I-MIBG]): >= 42 days must have elapsed from the last dose of systemically administered radiopharmaceutical therapy
Histone deacetylase (HDAC) inhibitors: Patients must not have received prior therapy with entinostat; patients who have received therapy with other HDAC inhibitors are eligible
Patients with known bone marrow metastatic disease will not be eligible
Exclusion Criteria
Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method both during and for 3 months after participation in this study; abstinence is an acceptable method of contraception; those who become pregnant while on treatment with entinostat must discontinue immediately and consult their treating physician
Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients requiring concurrent administration of valproic acid are not eligible for this trial
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
Patients with a BSA ? 1.17 m^2 at time of study enrollment are not eligible
Patients who are not able to swallow intact tablets are not eligible
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Patients with a history of allergy to medications that have a benzamide structure (e.g., metoclopramide, procarbazine, domperidone, cisapride etc.) are not eligible