A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
Condition: Acute Myelogenous Leukemia; High-Grade Myelodysplastic Syndrome
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome
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: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      This is an open-label, multicenter, phase 2 study of alisertib (MLN8237) in participants with
      acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
    

Eligibility criteria:

        Inclusion Criteria:

        Each participants must meet all of the following inclusion criteria:

          1. Male or female participants 18 years or older

          2. Eligible diagnoses:

               -  Acute myelogenous leukemia (except acute promyelocytic leukemia [APL]) with > 10%
                  bone marrow or peripheral blood blasts; failed to achieve complete response (CR)
                  or relapse after prior therapy, not candidates for potentially curative
                  treatment. Untreated participants > 60 are eligible if not candidates for
                  standard induction.

               -  High-grade myelodysplastic syndrome (MDS), defined by all the following features:
                  International Prognostic Scoring System (IPSS) Intermediate-2 or High Risk; > 10%
                  blasts on bone marrow examination; treatment failure from, or not candidates for,
                  standard therapies including demethylating agents, e.g. azacytidine or
                  decitabine.

          3. Eastern Cooperative Oncology Group performance status 0-2

          4. Female participants:

               -  Postmenopausal for at least one year

               -  Surgically sterile, or

               -  If childbearing potential, agree to practice two effective methods of
                  contraception or abstain from heterosexual intercourse.

          5. Male participants:

               -  Practice effective barrier contraception to one month after the last dose of
                  study drug, or

               -  Abstain from heterosexual intercourse.

          6. Voluntary written consent

          7. Participants on hydroxyurea may be included

        Exclusion Criteria:

          1. Pregnant or lactating females

          2. Known human immunodeficiency virus (HIV) positive or acquired immune deficiency
             syndrome (AIDS) - related illness

          3. Serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the protocol completion

          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 to 5 x the ULN if reasonably ascribed to underlying
             hematological disorder.

          6. Calculated creatinine clearance < 30 mL/minute

          7. Antineoplastic or radiotherapy within 14 days preceding the first dose

          8. 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

          9. Major surgery 14 days prior to the first dose

         10. Clinically uncontrolled central nervous system (CNS) involvement.

         11. Inability to swallow capsules

         12. History of uncontrolled sleep apnea or conditions that result in excessive daytime
             sleepiness, such as chronic lung disease