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

Location:

Jacksonville, Fla.

Trial status:

Open for Enrollment

Why is this study being done?

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.

Who is eligible to participate?

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 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

Last updated:

2/11/2014

NCT ID:

NCT01814826

IRB Number:

13-007425