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 enrollmentJanuary 21, 2021

DrugsVidaza Venclyxto

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: MILLENNIUM PHARMACEUTICALS, INC.
Enrollment: 150
Status: Active, not recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

January 21, 2021

End Date

TBD

Last Updated

4 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

MILLENNIUM PHARMACEUTICALS, INC.

Eligibility Criteria

Inclusion Criteria

•Male or female patients age \>\=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\.
•\- History of cardiac heart failure requiring treatment or ejection fraction \=\<55% or chronic stable angina.
•\- Carbon monoxide lung diffusion capacity (DLCO) \=\<65% or forced expiratory volume in 1 second (FEV1\) \=\<65% or significant history of chronic pulmonary obstructive disease.
•\- Any other patient’s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the project clinician before study enrollment.
•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):
•\- Total bilirubin \=\<1\.5 times the upper limit of the normal range (ULN) except in patients with Gilbert’s syndrome. Patients with Gilbert’s syndrome may enroll with direct bilirubin \=\<3 times the ULN of the direct bilirubin. Elevated indirect bilirubin due to posttransfusion hemolysis is allowed.

Exclusion 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.