Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
This phase I trial studies the side effects and the best dose of alisertib when given
 together with vorinostat in treating patients with Hodgkin lymphoma, B-cell non-Hodgkin
 lymphoma, or peripheral T-cell lymphoma that has come back. Alisertib and vorinostat may stop
 the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:

 I. To determine the maximum-tolerated dose (MTD) of MLN8237 (alisertib) when given in
 combination with vorinostat and to select a dose and schedule for further testing
 (recommended Phase 2 dose: RP2D) in patients with lymphoid malignancies.

 II. To describe the toxicities of MLN8237 when given in combination with vorinostat on a
 21-day schedule.

 III. To determine any clinical responses with MLN8237 in combination with vorinostat.

 IV. To compare the plasma pharmacokinetics of MLN8237 when given alone and in combination
 with vorinostat.

 V. To perform immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH)
 analysis to determine aurora kinase A (AURKA) expression in archival formalin-fixed
 paraffin-embedded sections from the most recent available tumor specimens of patients.

 VI. To perform correlative studies for apoptosis and proliferation on bone marrow and lymph
 node specimens, where available, obtained from patients in the expanded cohort at RP2D.

 OUTLINE: This is a dose-escalation study of alisertib.

 Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 or days 1-3 and 8-10,
 and vorinostat PO BID on days 1-14 or days 1-5 and 8-12. Courses repeat every 21 days in the
 absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up for at least 30 days.
Inclusion Criteria:

 -  Patients must have a histologically or cytologically confirmed lymphoid malignancy
 (like Hodgkin lymphoma or one of the mature B- or T-cell non-Hodgkin lymphomas as
 classified by World Health Organization [WHO]) for which standard curative or
 palliative measures do not exist or are no longer effective

 -  Patients must have measurable disease in two dimensions and >= 2 cm is acceptable (or
 1.5 cm if 0.5 slices are used, as in spiral computed tomography [CT] scans); lesions
 that are considered intrinsically non-measurable include the following:

 -  Bone lesions

 -  Leptomeningeal disease

 -  Ascites

 -  Pleural/pericardial effusion

 -  Inflammatory breast disease

 -  Lymphangitis cutis/pulmonis

 -  Abdominal masses that are not confirmed and followed by imaging techniques

 -  Cystic lesions

 -  Lesions that are situated in a previously irradiated area

 -  Patients must have had at least 1 prior systemic chemotherapy (not just steroids or
 local radiation); last chemotherapy or radiation must be at least 4 weeks prior to
 enrollment on this study; patients who decline other potentially curative therapy may
 be eligible; prior radiation therapy must not have been to more than 25% of the bone
 marrow; whole pelvic radiation is considered to be over 25%

 -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

 -  Life expectancy of greater than 12 weeks

 -  Absolute neutrophil count >= 1,500/mcL

 -  Platelets >= 100,000/mcL

 -  Total/direct bilirubin < 1.5 X institutional upper limit of normal; patients with
 elevation of indirect (unconjugated) bilirubin alone, as in Gilbert's syndrome, are
 eligible

 -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
 < 2.5 X institutional upper limit of normal

 -  Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60
 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

 -  Prior allogeneic stem cell transplant patients will be allowed to enroll if they are
 past day +100 of transplant, have no active graft-versus-host-disease, are not on any
 immunosuppressants and have been off immunosuppressants for at least 4 weeks; prior
 autologous stem cell transplant patients will also be allowed to enter this study if
 they are past their day +100 of transplant

 -  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, for
 the duration of study participation, and 4 months after completion of MLN8237
 administration; should a woman become pregnant or suspect she is pregnant while she or
 her partner is participating in this study, she should inform her treating physician
 immediately; men treated or enrolled on this protocol must also agree to use adequate
 contraception prior to the study, for the duration of study participation, and 4
 months after completion of MLN8237 administration

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

 -  According to current guidelines, patients must be able to take oral medication and to
 maintain a fast as required for 2 hours before and 1 hour after MLN8237
 administration; these guidelines may change pending results from an ongoing food
 effects study

 Exclusion Criteria:

 -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
 nitrosoureas or mitomycin C) prior to entering the study or those who have not
 recovered from adverse events due to agents administered more than 4 weeks earlier

 -  Patients who are receiving any other investigational agents

 -  Patients with known brain metastases should be excluded from this clinical trial

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to MLN8237, including but not limited to established allergic reaction to
 benzodiazepines

 -  Treatment with valproic acid within 14 days prior to initiation of study and during
 the study

 -  Prior use of valproic acid or any other histone deacetylase (HDAC) inhibitor for
 lymphoma treatment

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, 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 MLN8237

 -  Human Immunodeficiency virus (HIV)-positive patients on combination antiretroviral
 therapy are ineligible; appropriate studies will be undertaken in patients receiving
 combination antiretroviral therapy when indicated

 -  Known history of uncontrolled sleep apnea syndrome and other conditions that could
 result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary
 disease; requirement for supplemental oxygen; or any conditions that could result in
 excessive toxicity associated with the benzodiazepine-like effects of MLN8237

 -  Requirement for constant administration of proton pump inhibitor, histamine (H2)
 antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are
 allowed

 -  Inability to swallow oral medication or to maintain a fast as required for 2 hours
 before and 1 hour after MLN8237 administration or any condition that would modify
 small bowel absorption of oral medications, including malabsorption, or resection of
 pancreas or upper bowel

 -  Treatment with clinically significant enzyme inducers, such as the enzyme-inducing
 antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or
 phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days
 prior to the first dose of MLN8237 and during the study

 -  Patients with New York Heart Association (NYHA) class II-IV heart failure