A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome

• Status: Completed
• Trial end date: 2011-07-04
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Millennium Pharmaceuticals, Inc.

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