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

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00911066
• Other study ID #: C15003
• Status: Completed
• Phase: Phase 1
• First received: May 28, 2009
• Last updated: December 3, 2013
• Start date: June 2009
• Est. completion date: October 2013

Study information

• Verified date: December 2013
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Syndrome

Intervention

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)
• 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)

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Robert H. Lurie Comprehensive Cancer Center Northwestern University	Chicago	Illinois
United States	Institute for Drug Development	San Antonio	Texas
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements		12 months	Yes
Secondary	Pharmacokinetic parameters		12 months	No
Secondary	Pharmacodynamic effects		12 months	No
Secondary	Assess disease response		12 months	No
Secondary	Heart corrected QT intervals		During screening and during Cycle 1, Days 1 and 15	No