This trial is active, not recruiting.

Condition acute myelogenous leukemia
Treatment mln4924 and azacitidine
Phase phase 1
Target NAE
Sponsor Millennium Pharmaceuticals, Inc.
Start date April 2013
End date May 2016
Trial size 64 participants
Trial identifier NCT01814826, C15009


This study is an open-label, multicenter, phase 1b, dose-escalation study of MLN4924 in combination with azacitidine in adult patients with AML. The patient population will consist of patients 60 years of age or older, previously diagnosed with World Health Organization(WHO)-defined AML, who are unlikely to benefit from standard induction therapy and who have not received definitive treatment for AML or prior treatment with azacitidine or decitabine.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
mln4924 and azacitidine
MLN4924 (IV) and azacitidine (IV) in AML patients to determine maximum tolerated dose (MTD) on a 28-day cycle: Azacitidine Days 1, 2, 3, 4, 5, 8, 9 in Cycle 1 and for all subsequent cycles MLN4924 on Days 1, 3, and 5 for Cycle 1 and all subsequent cycles Both agents given on Days 1, 3, and 5 of Cycle 1 and all subsequent cycles

Primary Outcomes

Number of Adverse events
time frame: Recorded from the first dose of any study drug through 30 days (+ 10 days) after the last dose of study drug

Secondary Outcomes

Pharmacokinetic parameters including but not limited to AUC, Cmax, Systemic Clearance, Volume of Distribution, Elimination of Half-Life
time frame: Days 1 and 5 of Cycle 1
Disease response rate
time frame: Cycle 1 Day 22 and assessment of treatment-emergent resistance at Cycle 2 & Cycle 4 any time between Day 20 & Day 28. After Cycle 4, bone marrow assessments will be performed after completion of every third cycle (ie, Cycle 7, Cycle 10, etc.).
Thirty-day mortality rate
time frame: 30 days after the first dose of study drug on Cycle 1
60 Day Mortality Rate
time frame: 60 days after the first dose of study drug on Cycle 1

Eligibility Criteria

Male or female participants at least 60 years old.

Inclusion Criteria: - Patients with WHO-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following: 1. Greater than or equal to 75 years of age 2. Antecedent hematologic disease 3. Known adverse cytogenetic risk 4. Eastern Cooperative Oncology Group (ECOG) PS = 2 - Patient must not have received definitive treatment for AML, defined as any prior chemotherapy with antileukemic activity - ECOG PS 0 to 2 - Expected survival longer than 3 months from enrollment in the study - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence - Male patients who agree to practice effective barrier contraception or agree to practice true abstinence - Voluntary written consent must be given before performance of any study-related procedure - Suitable venous access for the study-required blood sampling - Adequate clinical laboratory values during the screening period as specified in the protocol - Able to undergo bone marrow aspiration and biopsy at screening Exclusion Criteria: - Previous treatment with azacitidine or decitabine - Known favorable cytogenetic risk - Any serious medical or psychiatric illness - Treatment with any investigational products - Known hypersensitivity to azacitidine or mannitol - Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis - Active uncontrolled infection or severe infectious disease - 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 - Known hepatic cirrhosis or severe pre-existing hepatic impairment - Known cardiac/cardiopulmonary disease - Left ventricular ejection fraction - Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis - Body mass index > 40 kg/m² - Treatment with CYP3A inducers within 14 days before the first dose of MLN4924 - Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea - Patients who are unwilling or unable to refrain from using hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) starting 5 days before the initial study drug administration and throughout the study will not be permitted to enroll

Additional Information

Official title A Phase 1b, Open-Label, Dose-Escalation Study of MLN4924 Plus Azacitidine in Treatment-Naïve Patients With Acute Myelogenous Leukemia Who Are 60 Years or Older
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Takeda.
Location data was received from the National Cancer Institute and was last updated in September 2016.