Pevonedistat + Belinostat for Acute Myeloid Leukemia or Myelodysplastic Syndrome

No longer recruiting at 5 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the side effects and optimal dose of two chemotherapy drugs, pevonedistat and belinostat, for individuals with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that have recurred or are unresponsive to treatment. These drugs aim to stop cancer cells from growing, dividing, or spreading. The trial may suit those diagnosed with AML or higher-risk MDS who have not responded to at least one previous treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that ongoing treatment with certain enzyme inducers and strong inhibitors of UGT1A1 is not allowed. It's important to discuss your current medications with the trial team to understand any potential interactions.

Is there any evidence suggesting that pevonedistat and belinostat are likely to be safe for humans?

Research shows that the combination of pevonedistat and belinostat is generally safe for adults with relapsed or hard-to-treat acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Studies have found that most people tolerate this treatment well, with side effects mainly affecting blood counts. While the treatment has shown some promise in fighting cancer, monitoring these blood-related side effects is important.

Prospective participants in a clinical trial with this treatment can find reassurance in the fact that previous patients have managed the side effects. However, as with any treatment, discussing potential risks with a doctor is crucial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pevonedistat and belinostat for treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) because it introduces a novel approach compared to standard treatments. Unlike traditional chemotherapies, which often target rapidly dividing cells indiscriminately, pevonedistat works by inhibiting a specific enzyme pathway crucial for cancer cell survival, potentially leading to more targeted cancer cell death. Belinostat, on the other hand, is a histone deacetylase inhibitor that can modify the expression of genes involved in cancer growth. Together, they offer a dual mechanism that might improve outcomes by attacking cancer cells in multiple ways, creating a promising potential for more effective and less toxic treatment options.

What evidence suggests that pevonedistat and belinostat might be effective for acute myeloid leukemia or myelodysplastic syndrome?

Research has shown that the combination of pevonedistat and belinostat, which trial participants will receive, may benefit patients with relapsed or hard-to-treat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Studies have found this treatment to be generally safe and capable of positively affecting the disease. In earlier research, some patients' conditions remained stable, meaning their disease did not worsen over time. This treatment aims to stop cancer cells from growing and dividing, helping to manage the disease. While the benefits are modest, the treatment's safety suggests it could be an option for those who haven't responded to other treatments.12367

Who Is on the Research Team?

KR

Keri R Maher

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.
My chronic hepatitis B is under control with undetectable viral load.
I am HIV positive with a good immune status, controlled virus, and no severe infections.
See 18 more

Exclusion Criteria

Ventricular rate < 50 bpm or > 120 bpm
I have a diagnosed heart condition known as long QT syndrome.
I will not donate sperm during the study or for 4 months after the last dose.
See 29 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post-treatment and then every 2 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

  • Belinostat
  • Pevonedistat
Trial Overview 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.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (belinostat, pevonedistat)Experimental Treatment2 Interventions

Belinostat is already approved in United States for the following indications:

🇺🇸
Approved in United States as Beleodaq for:

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Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

Belinostat is a small-molecule inhibitor that targets multiple classes of histone deacetylase enzymes and has been specifically developed for treating relapsed or refractory peripheral T-cell lymphoma (PTCL).
It has received accelerated approval from the FDA as a monotherapy for PTCL, marking a significant milestone in its development and offering a new treatment option for patients with this challenging condition.
Belinostat: first global approval.Poole, RM.[2021]

Citations

A phase I study of MLN4924 and belinostat in relapsed ...It also has been shown to exert single-agent activity in relapsed/refractory AML and myelodysplastic syndrome with some patients displaying stable disease over ...
NCT03772925 | Pevonedistat and Belinostat in Treating ...This phase I trial studies side effects and best dose of pevonedistat and belinostat in treating patients with acute myeloid leukemia or myelodysplastic ...
Pevonedistat plus belinostat in relapsed/refractory acute ...The combination of pevonedistat plus belinostat is safe in adult R/R AML with a manageable, primarily hematologic profile, and modest but notable activity.
Study Details | Pevonedistat and Belinostat in Treating ...An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...
5.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39821392/
A phase I study of MLN4924 and belinostat in relapsed ...The combination of pevonedistat plus belinosat is safe in an adult relapsed and/or refractory AML/High-Risk MDS population with modest but notable activity.
A phase I study of MLN4924 and belinostat in relapsed/ ...The combination of pevonedistat plus belinosat is safe in an adult relapsed and/or refractory AML/High-Risk MDS population with modest but notable activity.
Expanded safety analysis of pevonedistat, a first-in-class ...Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and ...
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