NCT03330821

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

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)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: University of Southern California · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. 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: I. 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: I. 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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IV
DRUG	Idarubicin	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Pevonedistat	Given IV
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2018-04-18
• Primary completion: 2026-06-30
• Completion: 2026-12-31
• First posted: 2017-11-06
• Last updated: 2025-12-04

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study