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Study Comparing Pevonedistat, Venetoclax, and Azacitidine with Venetoclax and Azacitidine in Adults with Acute Myeloid Leukemia Unfit for Intensive Chemotherapy

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a treatment for Acute Myeloid Leukemia (AML), a type of cancer that affects the blood and bone marrow. The study is comparing two treatment combinations. One group will receive a combination of three medications: Pevonedistat, Venetoclax, and Azacitidine. The other group will receive two medications: Venetoclax and Azacitidine. Pevonedistat is also known by its code name, MLN4924, and Venetoclax is sometimes referred to as ABT-199 or GDC-0199. Azacitidine is a medication used in various forms, including Azacitidine Mylan and Vidaza.

The purpose of this study is to determine if the combination of Pevonedistat, Venetoclax, and Azacitidine is more effective than the combination of Venetoclax and Azacitidine alone in treating adults with newly diagnosed AML who are not suitable for intensive chemotherapy. Participants in the study will be randomly assigned to one of the two treatment groups. The study will monitor the participants over a period of time to assess the effectiveness and safety of the treatments. The study will also look at how long participants live and how their disease responds to the treatment.

Participants will receive their assigned treatment and will be regularly monitored by healthcare professionals. The study will track various outcomes, including how long it takes for the disease to progress, the overall survival of participants, and the response of the leukemia to the treatment. The study aims to provide valuable information that could improve treatment options for patients with AML who cannot undergo intensive chemotherapy.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization

    Upon joining the study, participants are randomly assigned to one of two groups. This process is called randomization. It ensures that each participant has an equal chance of receiving either the combination of pevonedistat, venetoclax, and azacitidine or just venetoclax and azacitidine.

  2. Step 2

    Treatment initiation

    Participants begin their assigned treatment regimen. Those in the first group receive pevonedistat through an intravenous (IV) infusion. Venetoclax is taken orally in the form of film-coated tablets, and azacitidine is administered either intravenously or subcutaneously (under the skin).

    Participants in the second group take venetoclax orally and receive azacitidine either intravenously or subcutaneously.

  3. Step 3

    Treatment schedule

    The treatment is administered in cycles. Each cycle lasts 28 days. The specific dosage and frequency of each medication are determined by the study protocol and the participant's health condition.

  4. Step 4

    Monitoring and assessments

    Throughout the trial, participants undergo regular health assessments. These include blood tests, physical exams, and other necessary evaluations to monitor the effects of the treatment and ensure safety.

    Participants are closely monitored for any side effects or changes in their condition.

  5. Step 5

    End of treatment

    The treatment continues until the participant completes the study, experiences unacceptable side effects, or the disease progresses.

    At the end of the treatment, a final assessment is conducted to evaluate the participant's response to the therapy.

  6. Step 6

    Follow-up

    After completing the treatment, participants enter a follow-up phase. This involves periodic check-ups to monitor long-term health and any lasting effects of the treatment.

Who can join the trial?

15 criteria

  • Patients must be 18 years or older with newly diagnosed Acute Myeloid Leukemia (AML).
  • AML must be confirmed by a doctor using specific criteria.
  • Patients can have different types of AML, including:
    • Primary AML, which is newly diagnosed.
    • Secondary AML, which develops after other blood disorders or treatments.
    • Patients must be considered unfit for intensive chemotherapy due to age or other health issues, such as:
      • Being 75 years or older.
      • Being between 18 and 74 years old with at least one of the following conditions:
        • Poor physical health status (ECOG performance status of 2 or 3).
        • Severe heart problems, like heart failure or angina.
        • Severe lung problems, affecting breathing capacity.
        • Reduced kidney function (creatinine clearance less than 45 mL/min).
        • Liver problems with high bilirubin levels.
        • Laboratory test results must meet specific criteria, such as:
          • Total bilirubin within a certain range, except for patients with Gilbert's syndrome.
          • Liver enzymes (ALT and AST) within a certain range.
          • Kidney function (creatinine clearance) of at least 30 mL/min.
          • Albumin level greater than 2.7 g/dL.
          • White blood cell count must be less than 25 x 109/L. Patients who have reduced their white blood cell count with certain treatments may still qualify.

Who cannot join the trial?

9 criteria

  • Patients who have a different type of cancer other than Acute Myeloid Leukemia (AML) cannot participate.
  • Patients who are fit for intensive chemotherapy are not eligible.
  • Patients who have previously received treatment with the study drugs pevonedistat, venetoclax, or azacitidine are excluded.
  • Patients with uncontrolled or severe heart disease cannot join the study.
  • Patients with active infections that are not controlled are not allowed to participate.
  • Pregnant or breastfeeding women are not eligible for the study.
  • Patients with a history of severe allergic reactions to any of the study drugs are excluded.
  • Patients who have received another investigational drug within a certain period before the study cannot participate.
  • Patients with a history of other serious medical conditions that could interfere with the study are not eligible.
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Investigated drugs

  • Pevonedistat

    is an experimental drug being studied for its potential to treat certain types of cancer, including acute myeloid leukemia (AML). It works by blocking a specific protein in cancer cells, which may help stop the growth and spread of these cells. In this trial, pevonedistat is being tested to see if it can improve outcomes for patients with AML who cannot undergo intensive chemotherapy.

  • Venetoclax

    is a medication used to treat certain types of blood cancers, including AML. It works by targeting and blocking a protein that helps cancer cells survive. By inhibiting this protein, venetoclax can help kill cancer cells and slow down the progression of the disease. In this study, venetoclax is being used in combination with other treatments to see if it can improve patient outcomes.

  • Azacitidine

    is a medication used to treat certain blood disorders and types of leukemia, including AML. It works by interfering with the growth of cancer cells, which can help slow down or stop the progression of the disease. In this clinical trial, azacitidine is being used alongside other medications to evaluate its effectiveness in improving the health of patients with AML who are not suitable for intensive chemotherapy.

What is already known about the treatment

  • Pevonedistat

    Pevonedistat is administered intravenously, meaning it is given directly into a vein through an injection. It is currently being studied in clinical trials for its potential use in treating Acute Myeloid Leukemia (AML), particularly in patients who cannot undergo intensive chemotherapy. The main therapeutic indication for Pevonedistat is to improve event-free survival in AML patients. At the molecular level, Pevonedistat works by inhibiting a specific protein that helps cancer cells grow and divide, thereby slowing down or stopping the progression of the disease. It is classified as a targeted cancer therapy.

  • Venetoclax

    Venetoclax is taken orally in the form of a tablet. It is an established medication used in the treatment of certain types of leukemia, including Acute Myeloid Leukemia (AML), especially in patients who are not suitable for intensive chemotherapy. Venetoclax works by targeting and blocking a protein that helps cancer cells survive, leading to the death of these cells. It is classified as a BCL-2 inhibitor, which is a type of targeted cancer therapy.

  • Azacitidine

    Azacitidine is administered either as an injection under the skin or directly into a vein. It is a well-known medication used in the treatment of Acute Myeloid Leukemia (AML) and other blood disorders. Azacitidine works by incorporating into the DNA of cancer cells, disrupting their growth and leading to cell death. It is classified as a hypomethylating agent, which helps to restore normal function to genes that control cell growth.

Investigated diseases

Acute Myeloid Leukemia – Acute Myeloid Leukemia is a type of cancer that starts in the blood-forming cells of the bone marrow. It progresses rapidly, leading to the accumulation of immature white blood cells called myeloblasts. These cells crowd out normal blood cells, causing symptoms like fatigue, frequent infections, and easy bruising or bleeding. As the disease advances, it can spread to other parts of the body, including the lymph nodes, liver, and spleen. The rapid progression of the disease requires prompt medical attention to manage its effects.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2024-515424-36-00Protocol codePevonedistat-2002Estimated enrolment2 patientsSponsorTakeda Development Center Americas Inc.

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