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

This study has been completed.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc. Identifier:
First received: May 28, 2009
Last updated: December 3, 2013
Last verified: December 2013
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 Intervention Phase
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Drug: MLN4924
Drug: Azacitidine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacodynamic effects [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Assess disease response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Heart corrected QT intervals [ Time Frame: During screening and during Cycle 1, Days 1 and 15 ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: June 2009
Study Completion Date: October 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00911066

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.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT00911066     History of Changes
Other Study ID Numbers: C15003 
Study First Received: May 28, 2009
Last Updated: December 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 26, 2016