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Histone deacetylase inhibitor

Pevonedistat + Belinostat for Acute Myeloid Leukemia or Myelodysplastic Syndrome

Phase 1

Waitlist Available

Led By Steven Grant

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

If evidence of chronic HBV infection, HBV viral load must be undetectable on suppressive therapy, if indicated

Must not have

Known congenital long QT syndrome

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)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing pevonedistat and belinostat to see if they help leukemia or myelodysplastic syndrome that has come back or does not respond to treatment.

Who is the study for?

This trial is for adults with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who have tried at least one treatment before. They should not have a history of certain diseases, like AIDS or active hepatitis, and must be generally healthy with an ECOG performance status of <=2. Participants need to use effective contraception and understand the study's consent.

What is being tested?

The trial is testing the combination of two chemotherapy drugs, Pevonedistat and Belinostat, to determine their safety and optimal dosages in patients whose AML or MDS has returned after treatment or did not respond to previous treatments.

What are the potential side effects?

Potential side effects may include reactions related to the immune system, liver problems indicated by changes in blood tests, fatigue, nausea, vomiting, diarrhea, increased risk of infection due to low blood cell counts.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself but might not be able to do heavy physical work.

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My chronic hepatitis B is under control with undetectable viral load.

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I am HIV positive with a good immune status, controlled virus, and no severe infections.

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My kidney function, measured by creatinine clearance or GFR, is within the normal range.

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I can take care of myself but may not be able to do active work.

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My MDS is classified as intermediate-2 or high risk.

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I have AML, but not the APL type.

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My AML has not responded or has returned after treatment.

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My MDS is high risk and I didn't respond well to a previous treatment with a DNA-targeting drug.

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My kidney function, measured by creatinine clearance or GFR, is within the normal range.

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My condition did not improve after treatment with a specific type of medication.

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My AML has returned or didn't respond after at least one treatment.

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I had hepatitis C but have been treated and now have no detectable virus.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a diagnosed heart condition known as long QT syndrome.

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I will not donate eggs during the study or for 4 months after the last dose.

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I have leukemia that has spread to my brain.

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My condition is acute promyelocytic leukemia (APL).

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I have a bleeding disorder that is not under control.

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I don't have severe side effects from past treatments, except for those from hydroxyurea.

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I have a serious lung condition like COPD, lung scarring, or fibrosis.

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I haven't had major surgery in the last 28 days or minor surgery in the last 7 days.

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I do not have any uncontrolled illnesses or infections.

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I am taking or will take strong UGT1A1 inhibitors.

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I have a UGT1A gene variation.

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I have a serious irregular heartbeat.

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I am allergic to medications similar to MLN4924 or belinostat.

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I have had a stem cell transplant within the last 3 months.

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My heart's electrical cycle is longer than normal.

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I have been diagnosed with liver cirrhosis.

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I have been treated with belinostat or MLN4924 before.

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I am a candidate for a stem cell transplant that could potentially cure me.

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I have symptoms or signs of blood flow blockage or abnormal blood clotting.

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I do not have serious heart or lung conditions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Recommended phase 2 dose (RP2D) for the combination of MLN4924 (pevonedistat) and belinostat

Secondary study objectives

Change in MLN4924 (pevonedistat) and belinostat plasma concentrations

Change in candidate biomarker levels in bone marrow and/or blood samples

Duration of response

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (belinostat, pevonedistat)Experimental Treatment2 Interventions

Patients receive belinostat IV QD over 30 minutes on days 1-5 and pevonedistat IV QD over 60 minutes on days 1, 3, and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Belinostat

2006

Completed Phase 2

~430

Pevonedistat

2021

Completed Phase 3

~770