Health Trials

A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs)

ConditionsAccelerated Phase Myeloproliferative NeoplasmBlast Phase Myeloproliferative NeoplasmEssential ThrombocythemiaMyelodysplastic/Myeloproliferative NeoplasmMyeloproliferative Neoplasm, Not Otherwise SpecifiedPolycythemia VeraPrimary MyelofibrosisSecondary Myelofibrosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About 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.

Eligibility criteria

Qualifiers

Patients must have morphologically confirmed diagnosis of Philadelphia-chromosome negative MPN in accelerated-phase (10-19% myeloid blasts) or blast-phase (≥ 20% myeloid blasts) arising from polycythemia vera, essential thrombocythemia, primary myelofibrosis, secondary myelofibrosis, or MPN not otherwise specified, as per the World Health Organization (WHO) 2016 classification OR myelodysplastic syndrome (MDS)/MPN overlap syndromes (e.g., chronic myelomonocytic leukemia [CMML]) with ≥ 10% blasts

Patients must not have received prior DNMTi. Previous use of janus kinase (JAK) inhibition, hydroxyurea, and interferon is allowed. There is no required washout period for JAK inhibition and interferon

Age ≥ 18 years

Because no dosing or adverse event data are currently available on the use of ASTX727 (35 mg decitabine + 100 mg cedazuridine) in combination with iadademstat in patients < 18 years of age, children are excluded from this study

Disqualifiers

Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia

Patients who are receiving any other investigational agents or had received any investigational products within 3 weeks or 5 half-lives (whichever is shorter) prior to first dose of study treatment

Patients with a Fridericia's corrected QT interval (QTcF) > 450 ms

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727 (35 mg decitabine + 100 mg cedazuridine) or iadademstat

Trial design

Treatments tested in this trial

  • Biospecimen Collection
  • Bone Marrow Aspiration
  • Bone Marrow Biopsy
  • Decitabine and Cedazuridine
  • Iadademstat

Treatment groups

78 Participants
are divided into 2 treatment groups

Sponsors and collaborators

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov