Trials / Recruiting

RecruitingNCT06661915

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

A Randomized Phase 2 Trial of ASTX727 +/- Iadademstat in Accelerated/Blast-Phase Philadelphia Chromosome-Negative Myeloproliferative Neoplasms (MPNs)

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 62 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVE: I. To compare the acute leukemia response-complete (ALR-C) rate of iadademstat + ASTX727 (35 mg decitabine + 100 mg cedazuridine) and ASTX727 (35 mg decitabine + 100 mg cedazuridine) monotherapy within 4 cycles of therapy in patients with accelerated/blast-phase myeloproliferative neoplasms (MPN-AP/BP) previously untreated with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi). SECONDARY OBJECTIVE: I. To compare event-free survival (EFS), overall survival (OS), and percentage of patients going onto allogeneic hematopoietic stem cell transplant (allo-HCT) of iadademstat + ASTX727 (35 mg decitabine + 100 mg cedazuridine) and ASTX727 (35 mg decitabine + 100 mg cedazuridine) monotherapy in patients with MPN-AP/BP previously untreated with DNMTi. EXPLORATORY OBJECTIVES: I. To compare iadademstat target engagement between patients treated with iadademstat + ASTX727 (35 mg decitabine + 100 mg cedazuridine) and ASTX727 (35 mg decitabine + 100 mg cedazuridine) monotherapy by evaluating transcriptional changes in proliferative pathways implicated in MPN-AP/BP development and/or progression. II. To elucidate the common molecular pathways of resistance/progression in patients with MPN-AP/BP receiving DNMTi-based therapy. III. To measure response using the European LeukemiaNet 2022 Acute Myeloid Leukemia (AML) criteria (Döhner et al., 2022) and compare with the 2012 MPN-BP criteria that is being utilized for primary objective assessment. OUTLINE: This is a dose escalation study of ASTX727 and iadademstat followed by a randomized study. Patients are randomized to 1 of 2 arms. ARM I: Patients receive ASTX727 orally (PO) once daily (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. ARM II: 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. After completion of study treatment, patients who stop the study for reasons other than disease progression are followed up every 3 months. Patients who stop the study due to disease progression, are followed up every 6 months.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo buccal swab and blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
DRUG	Decitabine and Cedazuridine	Given PO
DRUG	Iadademstat	Given PO

Timeline

Start date: 2025-08-14
Primary completion: 2027-12-31
Completion: 2027-12-31
First posted: 2024-10-28
Last updated: 2026-04-13

Locations

26 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06661915. Inclusion in this directory is not an endorsement.