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MLN4924 for the Treatment of Acute Myelogenous Leukemia, Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00911066
Recruitment Status : Completed
First Posted : June 1, 2009
Last Update Posted : December 5, 2013
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

Brief Summary:
An open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with acute myelogenous leukemia (AML), high-grade myelodysplastic syndrome (MDS). The patient population will consist of adults previously diagnosed with AML including high-grade MDS for which standard curative, life-prolonging treatment does not exist or is no longer effective.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome Drug: MLN4924 Drug: Azacitidine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Dose Escalation, Phase 1 Study of MLN4924, a Novel Inhibitor of Nedd8-Activating Enzyme, in Adult Patients With Acute Myelogenous Leukemia,Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia
Study Start Date : June 2009
Actual Primary Completion Date : August 2013
Actual Study Completion Date : October 2013

Arm Intervention/treatment
Experimental: MLN4924 Drug: MLN4924

MLN4924 intravenous (IV) on a 21-day cycle on one of the following schedules:

  • Days 1, 3, and 5, followed by a rest period of 16 days (Schedule A)
  • Days 1, 4, 8, and 11, followed by a rest period of 10 days (Schedule B)
  • Continuous weekly dosing on Days 1, 8, and 15 (Schedule C)
  • Days 1, 4, 11, 15 for Cycle 1 only; Days 1, 4, 8, 11 for all subsequent cycles (Schedule D)
  • Dosing on Days 1, 3, and 5 in patients with high-grade MDS or AML (Schedule E)

Experimental: Azacitidine Drug: Azacitidine
Azacitidine will be administered (IV or subcutaneous (SC)) on Days 8 to 12 and Days 15 and 16 in Cycle 1, and on Days 1 to 5 and Days 8 to 9 (Schedule D)

Primary Outcome Measures :
  1. Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Pharmacokinetic parameters [ Time Frame: 12 months ]
  2. Pharmacodynamic effects [ Time Frame: 12 months ]
  3. Assess disease response [ Time Frame: 12 months ]
  4. Heart corrected QT intervals [ Time Frame: During screening and during Cycle 1, Days 1 and 15 ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Age greater than or equal to 18 years
  • Have the following diagnosis:

    • AML or ALL (for the dose escalation phase only)including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve complete response (CR) or who have relapsed after prior therapy and are not candidates for potentially curative treatment.
    • Acute Promyelocytic Leukemia (APL) patients are not eligible
    • AML or ALL patients who are over age 60 and have not received prior therapy are also eligible if they are not candidates for standard induction chemotherapy
    • High-grade MDS, defined as > 10% blasts on bone marrow examination
    • Low-grade MDS, defined as < 10% blasts on bone marrow examination (Schedule B expansion cohort only)
  • Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Female patients who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
  • Male patients who agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
  • Voluntary written consent
  • Suitable venous access
  • Adequate clinical laboratory values during the screening period as specified in the protocol
  • Patients who are on hydroxyurea may be included in the study and may continue on hydroxyurea while participating in this study.

Exclusion Criteria:

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period
  • Any serious medical or psychiatric illness
  • Treatment with any investigational products
  • Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea
  • Major surgery within 14 days before the first dose of study drug
  • Life-threatening illness unrelated to cancer
  • Clinically uncontrolled central nervous system (CNS) involvement
  • Known human immunodeficiency virus (HIV) positive
  • Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
  • Evidence of uncontrolled cardiovascular conditions as specified in the protocol
  • Diarrhea > Grade 1, based on the NCI CTCAE categorization
  • Systemic treatment with prohibited medications
  • Ongoing anticoagulant therapy (eg, aspirin, Coumadin, heparin) that cannot be held to permit bone marrow sampling
  • Use of acetaminophen, acetaminophen-containing products, and statins are not permitted on the day before dosing, day of dosing, and day after dosing with MLN4924

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 ClinicalTrials.gov identifier (NCT number): NCT00911066

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United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center Northwestern University
Chicago, Illinois, United States, 60657
United States, Maryland
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Texas
Institute for Drug Development
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
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Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00911066    
Other Study ID Numbers: C15003
First Posted: June 1, 2009    Key Record Dates
Last Update Posted: December 5, 2013
Last Verified: December 2013
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors