A Randomized, Open-label, Controlled, Phase 2 Study of Pevonedistat, Venetoclax, and Azacitidine Versus Venetoclax Plus Azacitidine in Adults With Newly Diagnosed Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy

Millennium Pharmaceuticals, Inc.0 sites150 target enrollmentApril 23, 2020

Overview

No summary available.

Registry

who.int

Start Date

April 23, 2020

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Sponsor

•Male or female patients aged \=18 years with newly diagnosed AML, morphologically confirmed (World Health Organization \[WHO] criteria 2008\). Patients may have newly diagnosed primary de novo AML or secondary AML (sAML) defined as AML after myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN), or therapy\-related AML (t\-AML) following cytotoxic therapy, and/or radiotherapy for a malignant or nonmalignant disease.
•To qualify for this study, a patient must be considered to be unfit for treatment with a standard Ara\-C and anthracycline induction regimen due to age or co\-morbidities defined by 1 of the following:
•\=75 years of age
•\=18 to \<75 years of age with at least one of the following:
•\- ECOG performance status of 2 or 3\.
•\- Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction \=50%, or chronic stable angina).
•\- Severe pulmonary disorder (eg, carbon monoxide lung diffusion
•capacity \=65% or forced expiratory volume in 1 second.
•\- Creatinine clearance \<45 mL/min (but \=30 mL/min as part of
•general eligibility criteria).

•History of myeloproliferative neoplasm with BCR\-ABL1 translocation or AML with BCR\-ABL1 translocation.
•Genetic diagnosis of acute promyelocytic leukemia.
•Extramedullary AML without evidence of bone marrow involvement.
•Prior treatment with hypomethylating agents for AML (treatment with hypomethylating agents for prior myelodysplastic syndromes \[MDS] is not exclusionary).
•Eligible for intensive chemotherapy and/or allogeneic stem cell transplantation.
•Patients with either clinical evidence of or history of central nervous system involvement by AML.
•Diagnosed or treated for another malignancy (except for adequately\-treated carcinoma in situ of any organ or nonmelanoma skin cancer) within 1 year before randomization or previously diagnosed with another malignancy and have any evidence of residual disease that may compromise the administration of pevonedistat, venetoclax or azacitidine. Prior MDS is also allowed, but the patient cannot have received treatment for MDS within 14 days before first dose of any study drug.
•Patient has a WBC count \=25 × 10^9/L.
•Patient with known hypersensitivity to pevonedistat, venetoclax, or azacitidine, and/or their excipients.
•Uncontrolled HIV infection.