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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00830518
Recruitment Status : Completed
First Posted : January 28, 2009
Last Update Posted : January 10, 2014
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia High-Grade Myelodysplastic Syndrome Drug: MLN8237 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
Study Start Date : February 2009
Actual Primary Completion Date : March 2010
Actual Study Completion Date : September 2011

Arm Intervention/treatment
Experimental: 1
Drug: MLN8237

MLN8237 will be administered orally (PO) at a dose of 50 mg twice daily (BID) for seven consecutive days followed by a 14-day rest period, in 21-day cycles. Dose reductions will be implemented in the setting of drug-related toxicities.

The first dose of MLN8237 on Cycle 1, Day 1 will be administered in the study clinic. Patients will continue to receive repeated cycles of MLN8237 treatment for up to 12 months, or until there is evidence of disease progression or unacceptable treatment-related toxicity. Treatment with MLN8237 may be continued beyond 12 months if it is determined that a patient would clearly derive benefit from continued therapy.

Primary Outcome Measures :
  1. Response rate: partial remission plus complete remission (PR + CR) [ Time Frame: Extent of disease measured by CBC with differential prior to every cycle, and bone marrow aspiration and biopsy at baseline, then bone marrow aspirate at end of Cycles 1 and 2, and then every other cycle (end of Cycles 4, 6, etc.). ]

Secondary Outcome Measures :
  1. Progression free survival (PFS) and duration of response (DOR) [ Time Frame: CBC prior to every cycle, bone marrow at baseline, end Cycles 1, 2, every other cycle. ]
  2. Safety and tolerability of MLN8237 treatment based on vital signs, physical examination, laboratory tests, and adverse events [ Time Frame: Duration of therapy through 30 days after the last dose. ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria:

  1. Male or female patients 18 years or older
  2. Eligible diagnoses:

    • Acute myelogenous leukemia (except APL) with > 10% bone marrow or peripheral blood blasts; failed to achieve CR or relapse after prior therapy, not candidates for potentially curative treatment. Untreated patients > 60 are eligible if not candidates for standard induction.
    • High-grade MDS, defined by all the following features: IPSS Intermediate-2 or High Risk; > 10% blasts on bone marrow examination; treatment failure from, or not candidates for, standard therapies including demethylating agents, eg azacytidine or decitabine.
  3. Eastern Cooperative Oncology Group perf. status 0-2
  4. Female patients:

    • 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 patients:

    • Practice effective barrier contraception to one month after the last dose of study drug, or
    • Abstain from heterosexual intercourse.
  6. Voluntary written consent
  7. Patients on hydroxyurea may be included

Exclusion Criteria:

  1. Pregnant or lactating females
  2. Known human immunodeficiency virus (HIV) positive or 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00830518

United States, New Jersey
Hematology and Oncology Associates of Northern New Jersey
Morristown, New Jersey, United States, 07962
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT00830518     History of Changes
Other Study ID Numbers: C14005
First Posted: January 28, 2009    Key Record Dates
Last Update Posted: January 10, 2014
Last Verified: December 2013

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions