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DNA methyltransferase inhibitor

Pevonedistat + Azacitidine/Decitabine + Venetoclax for Acute Myeloid Leukemia (PAVE Trial)

Phase 1

Waitlist Available

Led By Ehab Atallah, MD

Research Sponsored by Medical College of Wisconsin

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

During the dose-escalation phase, only subjects with relapsed/refractory AML will be eligible.

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to five years.

Awards & highlights

PAVE Trial Summary

This trial is testing a new drug to see what the best dose is and how well it works.

Who is the study for?

Adults diagnosed with Acute Myelogenous Leukemia (AML) who are either relapsed/refractory or newly diagnosed and can't have intensive chemotherapy. Participants need functioning kidneys, controlled blood cell counts, and normal clotting. They must not be pregnant or breastfeeding and agree to contraception if of childbearing potential.Check my eligibility

What is being tested?

The trial is testing the combination of Pevonedistat, Azacitidine (or Decitabine), and Venetoclax in patients with AML. It's a phase Ib study that starts by finding the right doses (dose escalation) followed by giving these doses to more people (dose expansion).See study design

What are the potential side effects?

Potential side effects may include nausea, vomiting, diarrhea, low blood cell counts leading to increased infection risk or bleeding problems, liver issues indicated by abnormal tests, fatigue, and possible allergic reactions.

PAVE Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My AML has returned or didn’t respond to treatment.

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I am able to care for myself and perform daily activities.

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I am a male and follow the required contraceptive measures.

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I have been diagnosed with AML or secondary AML according to WHO criteria.

PAVE Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to five years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to five years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to five years. for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Recommended phase 2 dose of pevonedistat when co-administered with azacitidine and venetoclax in patients with AML.

The toxicity profile of pevonedistat, azacitidine, and venetoclax combination therapy.

Secondary outcome measures

Complete Remission Rate

Complete Remission with Partial Hematological Recovery

Complete Remission without Minimal Residual Disease

+2 more

PAVE Trial Design

2Treatment groups

Experimental Treatment

Group I: Pevonedistat Dose EscalationExperimental Treatment3 Interventions

This study uses a varied 3 + 3 design. Three patients will be started at a dose of 10 mg/m^2 days 1, 3 and 5. If no DLTs are observed in the first 3 participants, then a new cohort will be enrolled at the next planned dose level of 15 mg/m^2 days 1, 3 and 5. If two out of three subjects experience a DLT, then they will de-escalate one dose level. If one subject in three experiences a DLT, then expand up to three subjects at 20 mg/m^2 day 1, 3 and 5. If two out of six subjects experience a DLT, de-escalate one level. All subjects will receive Azacitidine and Venetoclax at the indicated dosages and timing.

Group II: Dose Expansion PhaseExperimental Treatment3 Interventions

Patients will receive the recommended phase 2 dose (RP2D) identified from dose-escalation phase.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

FDA approved

Azacitidine

FDA approved

Pevonedistat

Not yet FDA approved

0 / 4Eligibility criteria met

Find a Location

Who is running the clinical trial?

Medical College of WisconsinLead Sponsor

609 Previous Clinical Trials

1,162,585 Total Patients Enrolled

Ehab Atallah, MDPrincipal InvestigatorMedical College of Wisconsin

9 Previous Clinical Trials

702 Total Patients Enrolled

Media Library

Azacitidine (DNA methyltransferase inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04172844 — Phase 1

Acute Myeloid Leukemia Research Study Groups: Dose Expansion Phase, Pevonedistat Dose Escalation

Acute Myeloid Leukemia Clinical Trial 2023: Azacitidine Highlights & Side Effects. Trial Name: NCT04172844 — Phase 1

Azacitidine (DNA methyltransferase inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04172844 — Phase 1

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

For what ailments is Venetoclax usually prescribed?

"Venetoclax has been approved for induction chemotherapy and is also used to treat a range of conditions, like refractory anemias, leukemia, myelocytic acute or multilineage dysplasia."

Answered by AI

How has the safety profile of Venetoclax been gauged in human trials?

"Due to a dearth of clinical data available, Venetoclax was given a score of 1 on our safety scale. This is because it is currently in Phase 1 trials and the efficacy has yet to be rigorously tested."

Answered by AI

Can you provide details about previous Venetoclax experiments?

"Currently, there are 348 Venetoclax trials in operation globally with 54 of those being Phase 3 studies. Of those running out of Toronto, Ontario specifically, 11251 locations have been established for study participation."

Answered by AI

To what extent is enrollment for this research project open?

"Sadly, this trial is no longer enrolling suitable candidates. It was first posted on January 13th 2020 and had its final update made in September 22nd 2022. For other studies related to leukemia, myelocytic acute - 1534 trials are actively recruiting patients - while Venetoclax has 348 active medical investigations available."

Answered by AI

Are there still opportunities to enroll in this medical trial?

"This trial is no longer accepting patients, with the last update occurring on September 22nd 2022. If you are in search of further studies, there are 1534 active trials for leukemias and myelocytic acute diseases as well as 348 clinical trials recruiting Venetoclax participants."

Answered by AI

What are the core aims of this medical experiment?

"This clinical trial will be evaluated over a span of up to 28 days for each cohort. The primary objective is to assess the toxicity profile of pevonedistat, azacitidine and venetoclax combination therapy. Secondary objectives include estimating overall survival through Kaplan-Meier methodology, assessing complete remission rate by determining bone marrow blast levels below 5%, platelet count exceeding 100x10^9/L (100,000/μL) and independence from red cell transfusions; as well as partial remission marrow status defined by reductions in baseline bone marrow blasts percentage above 50%."

Answered by AI

Recent research and studies

clinicaltrials.govStudy

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

Ehab L Atallah 2020. "Pevonedistat, Azacitidine (or Decitabine), and Venetoclax for the Treatment of Patients With Acute Myelogenous Leukemia". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04172844.

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