Alisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Condition: Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Waldenstrom Macroglobulinemia; Recurrence
Intervention: alisertib; rituximab; laboratory biomarker analysis
Intervention description: Given PO; Given IV; Laboratory correlative studies will be performed
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MLN8237; B-cell Non Hodgkin Lymphoma; Rituximab

Summary:

      This phase II trial studies how well alisertib with and without rituximab works in treating
      patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Alisertib may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal
      antibodies, such as rituximab, can block cancer growth in different ways. Some block the
      ability of cancer cells to grow and spread. Others find cancer cells and help kill them or
      carry cancer-killing substances to them. Giving alisertib with and without rituximab may be
      an effective treatment for B-cell non-Hodgkin lymphoma
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have histologically proven relapsed or refractory B-cell NHL of the following
             World Health Organization (WHO) classification subtypes: follicular lymphoma (FL),
             mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia
             (LPL/WM), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL),
             Burkitt's lymphoma (BL), and B-cell lymphoma with features unclassifiable between
             Burkitt's and large cell lymphoma; alternatively, patients with histologically proven,
             newly diagnosed transformed non-Hodgkin's lymphoma (tNHL) are eligible

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  At least one prior therapy; patients with newly diagnosed tNHL are eligible and do not
             need to have received prior therapy for the transformed lymphoma or prior indolent
             NHL; prior autologous stem cell transplant is allowed

          -  Serum creatinine =< 2.0 mg/dL

          -  Total bilirubin within normal limits

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x upper limit
             of normal

          -  Absolute neutrophil count (ANC) >= 1000/μL

          -  Platelet count >= 75,000/μL

          -  Recovery to =< grade 1 toxicities associated with prior therapy

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study

          -  Male subject agrees to use an acceptable method for contraception during the entire
             study treatment period through 4 months after the last dose of MLN8237

          -  Must be able to take oral medication and to maintain a fast as required for 2 hours
             before and 1 hour after MLN8237 administration

        Exclusion Criteria:

          -  Pregnant or breast-feeding women and women of childbearing age who are unwilling to
             use adequate contraception

          -  Patients with a history of central nervous system involvement by lymphoma

          -  Patients with known human immunodeficiency virus (HIV), hepatitis B or hepatitis C
             (active or carriers) are not eligible; this includes all patients with a positive
             hepatitis C antibody, hepatitis B surface antigen, or hepatitis B core antibody;
             previously vaccinated patients with positive hepatitis B surface antibody are eligible

          -  May not have received prior therapy with an Aurora kinase inhibitor

          -  Patients eligible for and willing to undergo autologous stem cell transplant with
             curative intent at the time of enrollment are not eligible; patients refractory to at
             least 2 prior regimens may enroll and proceed to curative autologous transplant if
             they respond

          -  Patients who are on chronic steroids for unrelated conditions (i.e. rheumatologic
             conditions) are not eligible if their total daily dose of steroids is equivalent to
             greater than 10 mg prednisone

          -  Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is
             considered to be over 25%

          -  Prior allogeneic bone marrow or organ transplantation

          -  If applicable, patient has >= grade 2 peripheral neuropathy within 14 days before
             enrollment

          -  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

          -  Patients who are on daily proton pump inhibitor therapy must be able to discontinue
             use or only require use of antacid or hydrogen (H2) antagonist intermittently;
             patients who require daily administration of proton pump inhibitor, H2 antagonist, or
             pancreatic enzymes are not eligible; intermittent uses of antacids or H2 antagonists
             are allowed

          -  Systemic infection requiring IV antibiotic therapy within 14 days preceding the first
             dose of study drug, or other severe infection

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities (except asymptomatic patients with
             a pacemaker with electrocardiogram (ECG) changes reflecting conduction abnormalities
             secondary to the pacemaker); prior to study entry, any ECG abnormality at screening
             has to be documented by the investigator as not medically relevant

          -  Female subject is pregnant or breast-feeding; confirmation that the subject is not
             pregnant must be established by a negative serum β-human chorionic gonadotropin
             (β-hCG) pregnancy test result obtained during screening; pregnancy testing is not
             required for post-menopausal or surgically sterilized women

          -  Patient has received other investigational drugs with 14 days before enrollment

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study

          -  Other severe acute or chronic medical or psychiatric condition, including uncontrolled
             diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement
             for pancreatic enzymes, any condition that would modify small bowel absorption of oral
             medications, or laboratory abnormality that may increase the risk associated with
             study participation or investigational product administration or may interfere with
             the interpretation of study results and, in the judgment of the investigator, would
             make the patient inappropriate for enrollment in this study

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

          -  Treatment with clinically significant enzyme inducers, such as the enzyme- inducing
             antiepileptic drugs phenytoin, carbamazepine 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 a corrected QT interval (QTc) at baseline of > 450 milliseconds or other
             factors that increase the risk of QT prolongation or arrhythmic events (i.e., heart
             failure, hypokalemia with potassium < 3.5 despite supplementation, family history of
             long QT syndrome) should be excluded

          -  Patients who require use of a concomitant medication that can prolong the QT interval
             and who are unable to discontinue use of this medication during the study period are
             excluded