Acute Myeloid Leukemia (AML) MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864 MedDRA version: 20.1 Level: LLT Classification code 10024330 Term: Leukemia acute System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10024348 Term: Leukemia myelogenous System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pevonedistat
Product Code: [MLN4924 (TAK-924)]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pevonedistat Hydrochloride
CAS Number: 1160295-21-5
Current
Sponsors
MILLENNIUM PHARMACEUTICALS, INC.
Eligibility
Sex/Gender
All
Inclusion 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 OR >=18 to =30 mL/minute (calculated by the Cockcroft-Gault formula). - Albumin >2.7 g/dL. • White blood cell count (WBC) =65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
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. • 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the combination of pevonedistat + venetoclax + azacitidine improves EFS compared with venetoclax + azacitidine in patients with newly diagnosed AML who are unfit for intensive chemotherapy. EFS is defined as the time from study randomization to the date of failure to achieve CR/CRi (ie, discontinuing treatment without achieving CR/CRi), relapse from CR or CRi, or death from any cause, whichever occurs first.;Secondary Objective: The key secondary objective is to determine whether the combination of pevonedistat + venetoclax + azacitidine improves OS when compared with venetoclax + azacitidine in an unfit population of patients with AML. (Please refer to protocol for detailed list of other secondary objectives);Primary end point(s): The primary endpoint of the study is EFS defined as failure to achieve CR/CRi, relapse from CR/CRi, or death. ;Timepoint(s) of evaluation of this end point: Up to 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoint is OS (Overall Survival) defined as the time from randomization to death from any cause. Other secondary endpoints: • 6-month, 1-year, and 2-year survival rates. • 30- and 60-day mortality rates defined as the proportion of patients who survive at most 30/60 days from the first dose of study drug(s). • Disease response rates as evaluated by IRC: – CR rate – CCR (CR + CRi) rate – ORR (CR + CRi + PR) rate – CR + CRh rate – Leukemia response rate (CR + CRi + PR + MLFS [marrow CR]) • Duration of CR, CRi, CCR, and ORR. • Time to first CR, CRi, and PR. • Time to relapse from CR/CRi or death, whichever occurs first. • HRQOL: Measured by the domains from EORTC-QLQ-C30, selected EORTC supplemental items, and EQ 5D-5L. • Pevonedistat plasma concentration data. • RBC and platelet transfusion independence rates for each arm. • Hospitalization rates for patients for each arm.;Timepoint(s) of evaluation of this end point: Up to 4 years | — |
Countries
Canada, France, Germany, Italy, Poland, United States
Contacts
Public ContactDrug Information Call Center
Millennium Pharmaceuticals, Inc., also known as Takeda Development Center Americas
Outcome results
None listed