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Acute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromePhase 1/2NCT03330821

Pevonedistat, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

A Phase 1/2 study testing Cytarabine, Idarubicin and Laboratory Biomarker Analysis in people with Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-Related Changes, run by University of Southern California at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase Ib/II trial studies the side effects and best dose of pevonedistat and to see how well it works in combination with cytarabine and idarubicin in treating patients with acute myeloid leukemia. Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cytarabine, Idarubicin and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
5 sitesUnited States
Study dates
18 Apr 2018to 31 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 1 highly effective method and 1 additional (barrier) of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] withdrawal, spermicides only and lactational amenorrhea are not acceptable methods of contraception)
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  • Male patients, even if surgically sterilized (ie, status postvasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] withdrawal, spermicides only and lactational amenorrhea are not acceptable methods of contraception)
  • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0-2
  • Expected survival > 3 months from study enrollment
  • Within 3 days before the first dose of study drug: albumin > 2.7 g/dL
  • Within 3 days before the first dose of study drug: total bilirubin < upper limit of normal (ULN)
  • Within 3 days before the first dose of study drug: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
  • Within 3 days before the first dose of study drug: creatinine clearance > 50 mL/min
  • Within 3 days before the first dose of study drug: hemoglobin > 8 g/dL (prior red blood cell [RBC] transfusion allowed); patients may be transfused to achieve this value; elevated indirect bilirubin due to post-transfusion hemolysis is allowed
  • Patients with previously untreated AML (except acute promyelocytic leukemia [APL]) who have at least one of the following:
  • Adverse genetic features as per the European Leukemia Net guidelines
  • Treatment related AML or AML with antecedent myelodysplastic syndrome (MDS); (patient who have received treatment with hypomethylating agents for MDS and have now transformed to AML are eligible)
  • Are over the age of 55 years and considered fit for chemotherapy
  • Patients with AML with MDS-related changes
  • Patients must be considered candidates for intensive chemotherapy treatment with standard doses of cytarabine and anthracycline regimen (?7+3 regimen?)
  • White blood cell (WBC) count < 50,000/uL before administration of pevonedistat on cycle 1 day 1; Note: hydroxyurea may be used to control the level of circulating leukemic blast cell counts to not lower than 10,000/uL during the study

Who cannot join

  • Known cardiopulmonary disease defined as one of the following:
  • Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
  • Cardiomyopathy or history of ischemic heart disease
  • Arrhythmia (eg, history of polymorphic ventricular fibrillation or torsade de pointes); however, patients with < grade 3 atrial fibrillation (a fib) for a period of at least 6 months may enroll; grade 3 a fib is symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker), or ablation; patients with paroxysmal a fib are permitted to enroll
  • Implantable cardioverter defibrillator
  • Congestive heart failure (New York Heart Association [NYHA] class III or IV; or class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 4 weeks before screening), myocardial infarction and/or revascularization (eg, coronary artery bypass graft, stent) within 6 months of first dose of study drug
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  • Patients who had ischemic heart disease who have had acute coronary syndrome (ACS), myocardial infarction (MI), and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll
  • Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)
  • Pulmonary hypertension
  • Prolonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelines
  • Left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiogram or radionuclide angiography
  • Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, and pulmonary fibrosis
  • Any serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with the completion of study procedures
  • Treatment with any investigational products within 14 days before the first dose of any study drug
  • Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug with the exception of: hydroxyurea (HU) in patients who need to continue this agent to maintain WBC count =< 50,000/mm^3
  • Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, septicemia, or methicillin resistant staphylococcus aureus infection
  • Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period
  • Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection
  • Life-threatening illness unrelated to cancer
  • Patients with uncontrolled coagulopathy or bleeding disorder
  • Known central nervous system (CNS) involvement
  • Known human immunodeficiency virus (HIV) seropositive
  • Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection
  • Note: patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment
  • Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of any study drug, except for hydroxyurea
  • Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this study
  • Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products
  • Patients with history of allergic or toxic reactions attributed to cytarabine or a history of allergic reactions to components of the formulated product
  • Patients with history of allergic or toxic reactions attributed to anthracyclines or a history of allergic reactions to components of the formulated product
  • Patients who have had prior chemotherapy for AML
  • Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s)
  • Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on day 1 before first dose of study drug (if applicable)
  • Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s)

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • University of Arizona Cancer Center - North Campus

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: Phase 1B/II Study of Escalating Doses of Pevonedistat (TAK-924, Formerly MLN4924) Administered in Combination With Standard Induction Chemotherapy (Cytarabine and Idarubicin) in Newly Diagnosed High Risk Acute Myelogenous Leukemia (AML)

This phase Ib/II trial studies the side effects and best dose of pevonedistat and to see how well it works in combination with cytarabine and idarubicin in treating patients with acute myeloid leukemia. Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Given pevonedistat, cytarabine, and idarubicin may work better in treating patients with acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of pevonedistat in combination with cytarabine and idarubicin in newly diagnosed high-risk acute myeloid leukemia. (Phase Ib) II. To determine the composite complete response rate (complete remission [CR] or complete remission with incomplete blood count recovery [CRi]) of pevonedistat in combination with cytarabine and idarubicin in newly diagnosed high-risk acute myeloid leukemia. (Phase II)

SECONDARY OBJECTIVES:

  1. To evaluate plasma pharmacokinetic (PK) profiles of pevonedistat when used in combination with cytarabine and idarubicin in the phase Ib part of the study.

II. To evaluate the relapse free (RFS), overall survival (OS), safety and tolerability of pevonedistat in combination with cytarabine and idarubicin in the phase II part of the study.

TERTIARY OBJECTIVES:

  1. To evaluate the pharmacodynamics (PD) effects of pevonedistat in combination with cytarabine and idarubicin in acute myelogenous leukemia (AML) blasts.

II. To evaluate potential predictive biomarkers of response to pevonedistat in combination with cytarabine and idarubicin in AML.

III. To determine the CR without minimal residual disease rate (CR MRD-) of pevonedistat in combination with cytarabine and idarubicin in newly diagnosed acute myeloid leukemia.

OUTLINE: This is a phase Ib, dose escalation study of pevonedistat followed by a phase II study.

INDUCTION: Patients receive idarubicin intravenously (IV) over 10-15 minutes on days 1-3, cytarabine IV over 1-3 hours on days 1-7, and pevonedistat IV over 60 minutes on days 1, 3, and 5. Patients with gross residual disease on day 14 bone marrow may receive a second course of induction chemotherapy.

CONSOLIDATION: Patients who achieve CR and will not undergo bone marrow transplant receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats every 28-35 days for 4 courses in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up for at least 30 days, and then every 3 months for 2 years.

Being tested
Cytarabine, Idarubicin, Laboratory Biomarker Analysis, Pevonedistat, Pharmacological Study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • IdarubicinDrug

    Also called 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PevonedistatDrug

    Also called MLN4924, Nedd8-Activating Enzyme Inhibitor MLN4924

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT03330821
Study groupRoleWhat they receive
Treatment (idarubicin, cytarabine, pevonedistat)ExperimentalINDUCTION: Patients receive idarubicin IV over 10-15 minutes on days 1-3, cytarabine IV over 1-3 hours on days 1-7, and pevonedistat IV over 60 minutes on days 1, 3, and 5. Patients with gross residual disease on day 14 bone marrow may receive a second course of induction chemotherapy. CONSOLIDATION: Patients who achieve CR and will not undergo bone marrow transplant receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats every 28-35 days for 4 courses in the absence of disease progression or unaccepted toxicity.
Receives: Drug: Cytarabine; Drug: Idarubicin; Other: Laboratory Biomarker Analysis; Drug: Pevonedistat; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite complete response rate

    Response will be assessed according to the 2017 European Leukemia Net Guidelines. The composite complete response rate will be calculated as the percentage of patients who have CR or CRi. Wilson 95% confidence interval will be provided.

    Measured: Up to 2 years

  2. Incidence of adverse events (Phase Ib)

    Will be assessed by Common Terminology Criteria for Adverse Events version 4.03.

    Measured: Up to 22 days

Secondary outcomes (1)

  1. Relapse-free survival (RFS)

    RFS will be calculated as the date of achievement of a remission (CR or CRi) until the date of relapse (documented morphological recurrence (≥ 5% blasts on in the bone marrow, reappearance of blasts in the blood or development of extramedullary disease after CR) or death - whichever comes first; patients who are alive and have not progressed or recurred at the time of their last disease assessment, will be censored at that time. Survival curves will be plotted by the Kaplan-Meier (KM) method. Median RFS and their 95% confidence intervals, 1-year and 2- year survival rates and corresponding standard errors will be derived from the KM curves.

    Measured: From the date of achievement of a remission until the date of relapse or death from any cause, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2017
  2. Study start18 Apr 2018
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03330821
Sponsor's protocol ID
9L-17-6
Other IDs
NCI-2017-01710, 9L-17-6, P30CA014089
Status last verified
May 2026
First submitted
31 Oct 2017
Last updated
1 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cytarabine, Idarubicin and Laboratory Biomarker Analysis in people with Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-Related Changes, run by University of Southern California at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite complete response rate (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03330821.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.

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