Phase 2
N=57
A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
Acute Myelogenous Leukemia · High-Grade Myelodysplastic Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT00830518 ↗Enrolled (actual)
57
Serious AEs
77.2%
Results posted
May 2018
Primary outcome: Primary: Best Overall Response Rate (ORR) Based on Investigator's Assessment — 6; 0; 1; 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Alisertib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Feb 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Best Overall Response Rate (ORR) Based on Investigator's Assessment |
6; 0; 1; 0; 5; 0 | — |
| SECONDARY Progression Free Survival (PFS) |
55.0; 38.0 | — |
| SECONDARY Duration of Response (DOR) |
409.0 | — |
| SECONDARY Best Overall Hematologic Improvement (HI) Response for Myelodysplastic Syndrome Based on Investigator Assessment |
0; 0; 0; 0; 91; 9 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths |
46; 11; 36; 8; 20; 2 | — |
| SECONDARY Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events |
12; 2; 10; 2; 8; 0 | — |
| SECONDARY Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events |
17; 4; 14; 3; 9; 2 | — |
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:
- Male or female participants 18 years or older
- 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.
- Eastern Cooperative Oncology Group performance status 0-2
- 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.
- Male participants:
- Practice effective barrier contraception to one month after the last dose of study drug, or
- Abstain from heterosexual intercourse.
- Voluntary written consent
- Participants on hydroxyurea may be included
Exclusion Criteria
- Pregnant or lactating females
- Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS) - related illness
- Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the protocol completion
- Total bilirubin > 1.5 × the upper limit of normal (ULN)
- 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.
- Calculated creatinine clearance < 30 mL/minute
- Antineoplastic or radiotherapy within 14 days preceding the first dose
- 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
- Major surgery 14 days prior to the first dose
- Clinically uncontrolled central nervous system (CNS) involvement.
- Inability to swallow capsules
- History of uncontrolled sleep apnea or conditions that result in excessive daytime sleepiness, such as chronic lung disease
Data sourced from ClinicalTrials.gov (NCT00830518). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.