ASTX727 + Iadademstat for Myeloproliferative Disorders

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antidepressants, 5HT2B/sigma drugs

Disqualifiers: IDH1-mutated MPN, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 16 weeks

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares the effect of ASTX727 in combination with iadademstat to ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). ASTX727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with iadademstat may be more effective than ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative MPNs.

Research Team

Anand A Patel

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

This trial is for adults with advanced Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) in accelerated or blast phase. Participants must have a specific level of disease severity, be able to perform basic activities (ECOG ≤ 3), and have normal organ function. Prior treatment with certain drugs is allowed, but not demethylating agents like DNMTi. People with well-managed HIV or hepatitis B can join.

Inclusion Criteria

I can care for myself but may spend a large part of the day in bed or sitting.

I have a specific type of blood cancer that is in an advanced stage.

I have not been treated with DNMTi before, but may have used JAK inhibitors, hydroxyurea, or interferon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ASTX727 with or without iadademstat in 28-day cycles

16 weeks

Multiple visits for blood sample collection and bone marrow aspiration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months if no disease progression, every 6 months if disease progression

Treatment Details

Interventions

• ASTX727
• Iadademstat

Trial Overview The study compares ASTX727 alone versus ASTX727 combined with iadademstat in treating MPNs. ASTX727 includes cedazuridine and decitabine, which help produce healthy blood cells and kill abnormal ones. Iadademstat may block enzymes that tumor cells need to grow.

Participant Groups

Group I: Arm II (ASTX727, iadademstat) Experimental Treatment 5 Interventions

Patients receive ASTX727 PO QD on days 1-5 and iadademstat PO QD on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo buccal swab sample collection at baseline and blood sample collection and bone marrow aspiration and biopsy throughout the study.

Group II: Arm I (ASTX727) Experimental Treatment 4 Interventions

Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo buccal swab sample collection at baseline and blood sample collection and bone marrow aspiration and biopsy throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+