A Clinical Study to Compare the Effectiveness and Safety of Pevonedistat, Venetoclax, and Azacitidine Versus Venetoclax Plus Azacitidine in Adults With Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy
- Conditions
- Acute Myeloid Leukemia (AML)MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864MedDRA version: 20.1Level: LLTClassification code 10024330Term: Leukemia acuteSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10024348Term: Leukemia myelogenousSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003117-33-FR
- Lead Sponsor
- Takeda Development Center Americas, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
• 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
OR
=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).
- Hepatic disorder with total bilirubin >1.5 times the upper limit of the normal range (ULN)
• 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.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0 times the ULN.
- Creatinine clearance =30 mL/minute (calculated by the Modification of Diet in Renal Disease Study equation).
- Albumin >2.7 g/dL.
• White blood cell count (WBC) <25 × 10^9/L. Patients who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria before starting therapy.
(Please refer to protocol for complete list of all inclusion criteria)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110
• 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.
• Patient is known to be positive for hepatitis B or C infection, with the exception of those with an undetectable viral load within 3 months.
• Known hepatic cirrhosis.
• Treatment with strong cytochrome P450 (CYP)3A4 inducers within 14 days before the first dose of the study drug.
• Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or ST elevation myocardial infarction within 6 months before first dose, or severe symptomatic pulmonary hypertension requiring pharmacologic therapy, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patient who has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, or cardiovascular disease that, in the medical judgement of the investigator, may compromise the delivery of pevonedistat, venetoclax, and/or azacitidine.
• Patients with uncontrolled coagulopathy or bleeding disorder.
(Please refer to protocol for complete list of all exclusion criteria)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method