Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma
Condition: Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma; Burkitt's Lymphoma; T-cell Lymphoma, Excluding Primary Cutaneous T-cell Lymphoma; Transformed Follicular Lymphoma With ≥ 50% Diffuse Large Cell Component
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell, Cutaneous
Intervention: Alisertib
Intervention description: Alisertib capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MLN8237; Alisertib; Drug therapy

Summary:

      The purpose of this study is to evaluate the anti-tumor activity of alisertib (MLN8237) in
      participants with relapsed or refractory non-hodgkin's lymphoma.
    

Eligibility criteria:

        Each participant must meet all of the following inclusion criteria to be enrolled in the
        study:

          1. Participant must have histological or cytological diagnosis of a hematological
             malignancy of the following types that has relapsed or was refractory to prior
             therapy:

               -  Diffuse large B-cell lymphoma

               -  Mantle cell lymphoma

               -  Burkitt's lymphoma

               -  Precursor B-lymphoblastic leukemia/lymphoma

               -  T-cell lymphoma, excluding primary cutaneous T-cell lymphoma

               -  Transformed follicular lymphoma with ≥ 50% diffuse large cell component.

          2. Male or female participants 18 years or older.

          3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          4. Measurable disease.

        Exclusion criteria include the following:

          1. Pregnant or lactating females.

          2. Known human immunodeficiency virus (HIV) positive or AIDS-related illness.

          3. Any serious medical or psychiatric illness that could interfere with the completion of
             treatment.

          4. Total bilirubin ≥ 1.5 × the upper limit of normal (ULN).

          5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2.5 × the ULN.
             AST, ALT may be elevated up to 5 times the ULN if their elevation can be reasonably
             ascribed to their underlying hematological disorder.

          6. Absolute neutrophil count (ANC) < 1,250/mm^3.

          7. Platelet count < 75,000/mm^3.

          8. Calculated creatinine clearance < 30 mL/minute.

          9. Autologous stem cell transplant less than 6 months prior to enrollment.

         10. Participants who have undergone allogeneic stem cell or organ transplantation.

         11. Systemic antineoplastic therapy including glucocorticoids (> 15 mg prednisone/day or
             equivalent), or treatment with an investigational agent within 14 days preceding the
             first dose of study drug treatment.

         12. Participants who have received treatment with nitrosoureas, mitomycin C, rituximab,
             alemtuzumab, or other unconjugated antibody treatment, within 12 weeks prior to first
             dose.

         13. Participants who have received treatment with radioimmunoconjugates or within 12 weeks
             prior to first dose.

         14. Participants who have received radiotherapy within 21 days prior to first dose.

         15. Myocardial infarction within 6 months of enrollment or current history of New York
             Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia.

         16. Major surgery within 14 days prior to the first dose.

         17. Infection requiring systemic antibiotic therapy within 14 days prior to the first dose
             or other serious infection.

         18. Clinically uncontrolled central nervous system (CNS) involvement.

         19. Inability to swallow capsules.

         20. History of uncontrolled sleep apnoea syndrome and other conditions that could result
             in excessive daytime sleepiness (eg, Chronic obstructive pulmonary disease - COPD).