An Efficacy and Safety Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine in Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML) and Low-Blast Acute Myelogenous Leukemia (AML)

Completed · Phase 2

Conditions studied: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute

In brief

The purpose of this study is to evaluate the efficacy and safety of pevonedistat plus azacitidine versus single-agent azacitidine in participants with HR-MDS or CMML, or low-blast AML.

Key facts

Study ID

NCT02610777

Run by

Millennium Pharmaceuticals, Inc.

People needed

120

Starts

2016-04-14

Expected to finish

2021-07-23

Last updated by the study team

2022-09-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female participants 18 years or older.
• Morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cells [WBC] <20,000 per microliter [/mcL]) or low blast AML based on 1 of the following:
• French American British (FAB) Classifications:
• Refractory anemia with excess blasts (RAEB) - defined as having 5% to 20% myeloblasts in the bone marrow.
• CMML with 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
• OR
• WHO Classifications:
• RAEB 1 - defined as having 5% to 9% myeloblasts in the bone marrow.
• RAEB 2 - defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
• CMML 2 - defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
• CMML 1 (Although CMML 1 is defined as having <10% myeloblasts in the bone marrow and/or <5% blasts in the blood, these participants may enroll only if bone marrow blasts >=5%.
• WHO defined AML with 20% to 30% myeloblasts in the bone marrow and <30% myeloblasts in peripheral blood who are deemed by the investigator to be appropriate for azacitidine based therapy.
• For MDS and CMML participants, prognostic risk category, based on the Revised International Prognostic Scoring System (IPSS R), of:
• Very high (>6 points),
• High (>4.5 to 6 points), or
• Intermediate (>3 to 4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Clinical laboratory values within the following parameters (repeat within 3 days before the first dose of study drug if laboratory values used for randomization were obtained more than 3 days before the first dose of study drug):
• Albumin >2.7 g/dL.
• Total bilirubin <upper limit of normal (ULN) except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin <=1.5*ULN of the direct bilirubin.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5*ULN.
• Creatinine clearance >=50 milliliter per minutes (mL/min).
• Hb >8 g/dL. Participants may be transfused to achieve this value. Elevated indirect bilirubin due to post transfusion hemolysis is allowed.
• For CMML participants: WBC count <20,000/mcL before administration of the first dose of study drug on Cycle 1 Day 1; participants must have been off hydroxyurea for at least 1 week prior to WBC count assessment.
• Ability to undergo the study required bone marrow sample collection procedures.

You may not qualify if…

• Previous treatment with decitabine or azacitidine or other hypomethylating agent.
• 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.
• Eligible for allogenic stem cell transplantation.
• Participants with MDS, CMML, or low blast AML, whose only site of disease is extramedullary, example, the skin.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures or could limit participant expected survival to less than 6 months.
• Treatment with any anti leukemic/anti MDS therapies (example, lenalidomide, cytarabine, anthracyclines, purine analogs) or with any investigational products within 14 days before the first dose of any study drug.
• Known hypersensitivity to mannitol.
• Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
• Major surgery within 14 days before first dose or a scheduled surgery during study period; insertion of a venous access device (example, catheter, port) is not considered major surgery.
• Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
• Life threatening illness unrelated to cancer.
• Prothrombin time (PT) or prolongation of the activated thromboplastin time (aPTT) >1.5 ULN or active uncontrolled coagulopathy or bleeding disorder.
• Known human immunodeficiency virus (HIV) seropositive.
• Known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (that is, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
• Known hepatic cirrhosis or severe pre-existing hepatic impairment.
• Known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association [NYHA] Class III or IV) and/or myocardial infarction within 6 months prior to first dose, or severe pulmonary hypertension. As an example, well controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion.
• Treatment with strong cytochrome P450 (CYP) 3A inhibitors or inducers within 14 days before the first dose of study drug.
• Systemic antineoplastic therapy or radiotherapy for other malignant conditions within 12 months before the first dose of any study drug, except for hydroxyurea.
• Female participants who are lactating and breast feeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
• Female participants who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
• Male participants who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).

Where it is running

• Greenville Health System — Little Rock, Arkansas, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Compassionate Cancer Care Medical Group Incorporated — Riverside, California, United States
• Rocky Mountain Cancer Centers — Aurora, Colorado, United States
• Smilow Cancer Center at Yale New Haven Hospital — New Haven, Connecticut, United States
• University of Miami Miller School of Medicine — Miami, Florida, United States
• H Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States
• University of Chicago Medical Center — Chicago, Illinois, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• San Juan Oncology Associates — Farmington, New Mexico, United States
• Monter Cancer Center — Lake Success, New York, United States
• Weill Cornell Medical College — New York, New York, United States
• Columbia University Medical Center — New York, New York, United States
• University of Rochester Medical Center — Rochester, New York, United States
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Cancer Care Center of South Texas — New Braunfels, Texas, United States
• Nebraska Cancer Specialists — The Woodlands, Texas, United States
• Texas Oncology - Waco, TX — Tyler, Texas, United States
• University of Virginia — Charlottesville, Virginia, United States
• Medical Oncology Associates — Spokane, Washington, United States
• Yakima Valley Memorial Hospital — Yakima, Washington, United States
• AZ Sint-Jan AV — Bruges, West-Vlaanderen, Belgium
• Grand Hopital de Charleroi asbl — Charleroi, Belgium
• University of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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