Pevonedistat + Decitabine for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Hydroxyurea

Must not be taking: CYP3A4/5 inducers

Disqualifiers: Active malignancies, Cardiopulmonary disease, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of pevonedistat when given together with decitabine in treating patients with high risk acute myeloid leukemia. Pevonedistat and decitabine may stop the growth of cancer cells by blocking some of the enzymes need for cell growth.

Research Team

Guido Marcucci

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults aged 60 or older with high-risk acute myeloid leukemia (AML), either newly diagnosed, untreated and not candidates for standard chemotherapy, or those with relapsed/refractory disease. It includes younger AML patients unfit for stem cell transplant. Participants must have a life expectancy over 6 months, be able to perform daily activities (ECOG <=2), and use effective contraception if of childbearing potential.

Inclusion Criteria

You are 60 years or older and your disease has come back or is not responding to treatment.

If you have cancer cells that have spread outside of your bone marrow, you may still be eligible for the study if you meet other criteria.

You have other medical conditions, but they are not expected to shorten your life expectancy within the next six months.

Exclusion Criteria

You do not have any other active cancer except for certain types that have been cured or treated a long time ago.

You have a serious medical or mental health condition that could affect your ability to participate in the study.

You have not taken any experimental medications within the 2 weeks before starting the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive pevonedistat IV over 1 hour on days 1, 3, and 5 and decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unexpected toxicity.

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Monthly for 1 year, bi-monthly for another year

Treatment Details

Interventions

• Decitabine
• Pevonedistat

Trial Overview The study is testing the combination of two drugs: pevonedistat and decitabine, to determine their safety and optimal dosages in treating high-risk AML. The goal is to see if these drugs can halt cancer growth by inhibiting enzymes necessary for cell proliferation.

Participant Groups

Group I: Treatment (pevonedistat, decitabine) Experimental Treatment 4 Interventions

Patients receive pevonedistat IV over 1 hour on days 1, 3, and 5 and decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unexpected toxicity.

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+