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

NCT03330821 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 9L-17-6NCI-2017-01710P30CA014089
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Therapy-Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 2 years

• Incidence of adverse events (Phase Ib)

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

  Up to 22 days

Secondary Outcomes (1)

• Relapse-free survival (RFS)

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

Study Arms (1)

Treatment (idarubicin, cytarabine, pevonedistat)

EXPERIMENTAL

INDUCTION: 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.

Drug: Cytarabine; Drug: Idarubicin; Other: Laboratory Biomarker Analysis; Drug: Pevonedistat; Other: Pharmacological Study

Interventions

Cytarabine DRUG

Given IV

Also known as: .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, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (idarubicin, cytarabine, pevonedistat)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

Treatment (idarubicin, cytarabine, pevonedistat)

Pevonedistat DRUG

Given IV

Also known as: MLN4924, Nedd8-Activating Enzyme Inhibitor MLN4924

Treatment (idarubicin, cytarabine, pevonedistat)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (idarubicin, cytarabine, pevonedistat)

Pharmacological Study OTHER

Correlative studies

Treatment (idarubicin, cytarabine, pevonedistat)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85724, United States

Location

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Interventions

Cytarabine; Idarubicin; pevonedistat

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Kevin Kelly, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 6, 2017
• Study Start: April 18, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

US (5)