NCT04172844

Pevonedistat, Azacitidine (or Decitabine), and Venetoclax for the Treatment of Patients With Acute Myelogenous Leukemia

A Multisite Phase Ib Study of Pevonedistat, Azacitidine (or Decitabine), and Venetoclax (PAVE) for the Treatment of Patients With Acute Myelogenous Leukemia (AML)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase Ib study with a 3 + 3 dose escalation design followed by a dose-expansion phase.

Detailed description

The study hypothesis is that the combination of pevonedistat, azacitidine, and venetoclax will be effective, safe, and well tolerated in patients with AML. The primary objective of this portion of the study is to determine a recommended phase 2 dose (RP2D) of pevonedistat, azacitidine, and venetoclax. The investigators will use a variation of the 3+3 design where both escalation and de-escalation are possible. A minimum of nine and a maximum of 24 subjects will be needed for the phase 1 part of the study (dose-escalation phase). The dose limiting toxicity (DLT) observation period for dose escalation will be during cycle 1. Prior to enrolling patients at the next applicable dose level, all patients must complete the DLT period of the current dose level. The Data Safety Monitoring Committee will review the results of each dose level before the next applicable dose level opens for enrollment. Dose Expansion Phase The primary objective of this portion of the study is to confirm the feasibility and tolerance of the combination of pevonedistat, azacitidine, and venetoclax in patients with AML. Given that the dose-escalation phase described above will be able to establish the RP2D, the dose-expansion phase will employ this dose. In addition to relapsed/refractory AML patients, newly diagnosed AML patients can also be included in this phase to assess the feasibility and tolerance of this combination regimen. A minimum of six patients will be enrolled in the dose-expansion phase, which could be expanded based on the safety and tolerability.

Conditions

• Acute Myelogenous Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	75mg/m\^2 Days 1-7 given IV
DRUG	Venetoclax	100 mg on cycle 1 day 1, 200 mg daily on cycle 1 day 2, 400 mg on cycle 1 day 3 and thereafter from cycle 1. Venetoclax is given for a minimum of 21 days and a maximum of 28 days. Administered orally.
DRUG	Pevonedistat	The doses for the 3 + 3 design (dose escalation phase) are listed in the arm description. The dose-expansion phase will use the maximum-tolerated dose.

Timeline

• Start date: 2020-01-13
• Primary completion: 2021-12-12
• Completion: 2022-02-27
• First posted: 2019-11-21
• Last updated: 2024-06-04

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study