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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00830518
First received: January 27, 2009
Last updated: December 10, 2013
Last verified: December 2013

January 27, 2009
December 10, 2013
February 2009
March 2010   (final data collection date for primary outcome measure)
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.). ] [ Designated as safety issue: No ]
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, end of Cycles 1 and 2, and then every other cycle (end of Cycles 4, 6, etc.). ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00830518 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
A Phase 2 Trial of MLN8237 in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome

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

Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myelogenous Leukemia
  • High-Grade Myelodysplastic Syndrome
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.

Experimental: 1
MLN8237
Intervention: Drug: MLN8237
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
57
September 2011
March 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00830518
C14005
No
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP