30 Participants Needed

Pevonedistat + Belinostat for Acute Myeloid Leukemia or Myelodysplastic Syndrome

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)

Trial Summary

What is the purpose of this trial?

This phase I trial studies side effects and best dose of pevonedistat and belinostat in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as pevonedistat and belinostat, 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.

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.

What data supports the effectiveness of the drug combination Pevonedistat and Belinostat for treating Acute Myeloid Leukemia or Myelodysplastic Syndrome?

Research shows that the combination of Pevonedistat and Belinostat can effectively kill leukemia cells by disrupting their DNA repair processes, leading to cell death. This combination has shown promise in reducing tumor burden and improving survival in animal models, suggesting potential benefits for patients with these conditions.12345

What is known about the safety of Pevonedistat and Belinostat in humans?

Belinostat has been tested in humans for various blood cancers, showing some serious side effects like low blood cell counts, fatigue, and headaches. Pevonedistat has been studied in other trials, but specific safety data for this combination in humans is limited.56789

What makes the drug combination of Pevonedistat and Belinostat unique for treating acute myeloid leukemia or myelodysplastic syndrome?

The combination of Pevonedistat and Belinostat is unique because Pevonedistat inhibits a key enzyme involved in protein degradation, which affects cell growth and survival, while Belinostat is an HDAC inhibitor that affects gene expression and promotes cancer cell death. This dual approach targets different mechanisms in cancer cells, potentially offering a novel treatment option for these conditions.13678

Research Team

KR

Keri R Maher

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Eligibility Criteria

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.
Your bilirubin levels should be within the normal range unless you have Gilbert's syndrome. If you have Gilbert's syndrome, your direct bilirubin levels should not be more than 1.5 times the upper limit of normal for the laboratory.
See 18 more

Exclusion Criteria

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

Timeline

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

Treatment Details

Interventions

  • Belinostat
  • Pevonedistat
Trial OverviewThe 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.
Participant Groups
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.

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

🇺🇸
Approved in United States as Beleodaq for:
  • Peripheral T-cell lymphoma (PTCL)

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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]

References

Feasibility of pevonedistat combined with azacitidine, fludarabine, cytarabine in pediatric relapsed/refractory AML: Results from COG ADVL1712. [2023]
Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. [2021]
Belinostat: first global approval. [2021]
The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR. [2021]
A phase I clinical trial of the histone deacetylase inhibitor belinostat in patients with advanced hematological neoplasia. [2014]
Epigenetic and molecular mechanisms underlying the antileukemic activity of the histone deacetylase inhibitor belinostat in human acute promyelocytic leukemia cells. [2021]
A phase 2 study of belinostat (PXD101) in patients with relapsed or refractory acute myeloid leukemia or patients over the age of 60 with newly diagnosed acute myeloid leukemia: a California Cancer Consortium Study. [2021]
Phase 1 dose-escalation study of oral abexinostat for the treatment of patients with relapsed/refractory higher-risk myelodysplastic syndromes, acute myeloid leukemia, or acute lymphoblastic leukemia. [2019]
Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS). [2021]