Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

Pevonedistat

Antimetabolites

Enzyme Inhibitors

MLN4924 intravenously (IV) in AML participants in a 28-day cycle:

* MLN4924 on Days 1, 3, and 5 for Cycle 1 and all subsequent cycles

MLN4924

Azacitidine (IV) or subcutaneously in AML participants in a 28-day cycle:

- Azacitidine Days 1, 2, 3, 4, 5, 8, 9 in Cycle 1 and for all subsequent cycles

Medical Monitor

The purpose of this study is to establish the maximum tolerated dose (MTD), and to assess the safety and tolerability of MLN4924 (pevonedistat) in combination with azacitidine in treatment naive participants with AML who were 60 years of age or older.

Study of MLN4924 Plus Azacitidine in Treatment-naive Participants With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older

A Phase 1b, Open-Label, Dose-Escalation Study of MLN4924 Plus Azacitidine in Treatment-Naïve Patients With Acute Myelogenous Leukemia Who Are 60 Years or Older

Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Disease response was based on best overall response as determined by an investigator based on revised recommendations of the International Working Group (IWG) Response Criteria for AML. Best overall response rate was defined as percentage of participants who had complete response (CR), partial response (PR), or CR/remission with incomplete blood count recovery (Cri). CR: free of leukemia-related symptoms, absolute neutrophil count (ANC) greater than (\>)1.0\*10\^9 per liter (/L), platelet count greater than or equal to (\>=) 100\*10\^9/L, normal bone marrow with \<5 percent (%) blasts and no Auer rods. CRi: As per CR but with residual thrombocytopenia (platelet count \<100\*10\^9/L) or residual neutropenia (ANC \<1.0\*10\^9/L). PR: \>=50% decrease bone marrow blasts to 5 to 25% abnormal cells, or CR with less than or equal to (\<=) 5% blasts if Auer rods present.

The duration of response was defined in participants with disease response (CR, CRi, or PR) as the time between the first documentation of response and disease progression. Duration of response was determined by an investigator based on revised recommendations of the IWG Response Criteria for AML. CR: free of leukemia-related symptoms, absolute neutrophil count (ANC) greater than (\>)1.0\*10\^9 per liter (/L), platelet count greater than or equal to (\>=) 100\*10\^9/L, normal bone marrow with \<5 percent (%) blasts and no Auer rods. CRi: As per CR but with residual thrombocytopenia (platelet count \<100\*10\^9/L) or residual neutropenia (ANC \<1.0\*10\^9/L). PR: \>=50% decrease bone marrow blasts to 5 to 25% abnormal cells, or CR with less than or equal to (\<=) 5% blasts if Auer rods present.

Overall survival was defined as the time from the first dose of study drug to the date of death. The Kaplan-Meier method was used to estimate overall survival, along with the corresponding 95% confidence interval.

Millennium Pharmaceuticals, Inc.

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

MLN4924 20 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m\^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or progressive disease (PD), or until treatment was discontinued for another reason (up to Cycle 53).

MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous

MLN4924 20 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m\^2, infusion, subcutaneously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

MLN4924 20 mg/m^2 + Azacitidine 75 mg/m^2 Subcutaneous

MLN4924 30 mg/m\^2, infusion, intravenously, once on Days 1, 3, and 5 in combination with azacitidine 75 mg/m\^2, infusion, intravenously, once on Days 1 through 5, 8 and 9 before administration of MLN4924 in a 28-day treatment cycle up to symptomatic deterioration or PD, or until treatment was discontinued for another reason (up to Cycle 53).

MLN4924 30 mg/m^2 + Azacitidine 75 mg/m^2 Intravenous

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body Surface Area (BSA)

The safety population was defined as all enrolled participants who receive at least 1 dose of any study drug, MLN4924 or azacitidine.

Medical director

TEAEs

SAEs

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Blood creatinine increased

Proteinuria

Blood urea increased

Renal impairment

Blood bilirubin increased

Aspartate aminotransferase increased

Alanine aminotransferase increased

Gamma-glutamyltransferase increased

Blood alkaline phosphatase increased

Anaemia

Neutropenia

Leukopenia

Febrile neutropenia

Neutrophil count decreased

Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings

Tachycardia

Hypotension

Orthostatic Hypotension

Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings

Cycle 1 Day 1

Cycle 1 Day 5

The pharmacokinetic (PK)-evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and MLN4924 concentration-time data to reliably estimate PK parameters. The PK population where data at specified time points was available.

Dose-escalation Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924

The PK-evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and MLN4924 concentration-time data to reliably estimate PK parameters. The PK population where data at specified time points was available.

Maximum Tolerated Dose (MTD) Expansion Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924

Cycle Day 5

Dose-escalation Phase, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN4924

MTD Expansion Phase, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN4924

Dose-escalation Phase, Ctrough: Observed Plasma Concentration at the End of the Dosing Interval for MLN4924

MTD Expansion Phase, Ctrough: Observed Plasma Concentration at the End of the Dosing Interval for MLN4924

Dose-escalation Phase, AUC0-tau: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (Tau) for MLN4924

MTD Expansion Phase, AUC0-tau: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (Tau) for MLN4924

Dose-escalation Phase, AUC24hours: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-Dose for MLN4924

MTD Expansion Phase, AUC24hours: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-Dose for MLN4924

Dose-escalation Phase, AUCinf: Area Under the Plasma Concentration-time Curve Extrapolated to Infinity for MLN4924

MTD Expansion Phase, AUCinf: Area Under the Plasma Concentration-time Curve Extrapolated to Infinity for MLN4924

Dose-escalation Phase, Lambdaz: Terminal Disposition Phase Rate Constant for MLN4924

MTD Expansion Phase, Lambdaz: Terminal Disposition Phase Rate Constant for MLN4924

Dose-escalation Phase, t1/2: Terminal Disposition Phase Half-life for MLN4924

MTD Expansion Phase, t1/2: Terminal Disposition Phase Half-life for MLN4924

Dose-escalation Phase, Rac: Observed Accumulation Ratio for MLN4924

MTD Expansion Phase, Rac: Observed Accumulation Ratio for MLN4924

Dose-escalation Phase, CLp: Systemic Clearance for MLN4924

MTD Expansion Phase, CLp: Systemic Clearance for MLN4924

Dose-escalation Phase, Vss: Volume of Distribution at Steady-state for MLN4924

MTD Expansion Phase, Vss: Volume of Distribution at Steady-state for MLN4924

The response-evaluable population was defined as all participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Participants who were evaluable at a particular time point for this outcome measure were included in the assessment.

Best Overall Response Rate

Duration of Response

Overall Survival

Thirty-day Mortality Rate

No participant was analyzed since this outcome measure was not planned to be assessed but added in the protocol summary by error.

Sixty-day Mortality Rate

Overall Study

Spots Global Cancer Trial Database for Study of MLN4924 Plus Azacitidine in Treatment-naive Participants With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial