Recruiting

Phase 2

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

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06661915

Conditions

Accelerated Phase Myeloproliferative Neoplasm

Blast Phase Myeloproliferative Neoplasm

Essential Thrombocythemia

Myelodysplastic/Myeloproliferative Neoplasm

Myeloproliferative Neoplasm, Not Otherwise Specified

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Decitabine and Cedazuridine

Iadademstat

Study Details

Brief 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.

Conditions

Accelerated Phase Myeloproliferative Neoplasm

Blast Phase Myeloproliferative Neoplasm

Essential Thrombocythemia

Myelodysplastic/Myeloproliferative Neoplasm

Myeloproliferative Neoplasm, Not Otherwise Specified

Study ID

NCT06661915

Start date

Aug 14, 2025

Status verified date

Aug, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 (Karnofsky ≥ 30)
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (unless elevated due to Gilbert's syndrome, thought to be related to MPN-AP/BP, or due to extrasvascular hemolysis. In these cases conjugated bilirubin should be ≤ 2.0 x ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 by Modification of Diet in Renal Disease (MDRD)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
The effects of ASTX727 (35 mg decitabine + 100 mg cedazuridine) and/or iadademstat on the developing human fetus are unknown. For this reason and because DNMT inhibitor and LSD1 inhibitor agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and 6 months after completion of ASTX727 (35 mg decitabine + 100 mg cedazuridine) and/or iadademstat administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and 6 months after completion of ASTX727 (35 mg decitabine + 100 mg cedazuridine) and/or iadademstat administration
Women of child-bearing potential must agree not to donate or freeze egg(s) during the course of this study or within 180 days after receiving their last dose of study drug. Male patients must agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Patient is able to swallow oral medications
Patients must have a body weight of at least 50 kg due to the use of flat doses. If a patient is on continued treatment and is receiving benefit, but falls below 50 kg, they may stay on the study per investigator discretion. Otherwise, they will have to come off the study
Peripheral white blood cell (WBC) count < 25 x 10\^9/L on day 1 prior to treatment initiation. Hydroxyurea is allowed for cytoreduction until 24 hours prior to study treatment. Hydroxyurea may be resumed during cycle 1 if WBC count rises above 25 x 10\^9/L. Use of hydroxyurea beyond cycle 1 should be discussed with study chair

Exclusion Criteria:

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
Patients medicated with anti-depressants reported to have KDM1A/LSD1 inhibitory activity: tranylcypromine or phenelzine
Patients with IDH1-mutated MPN blast phase (≥ 20% blasts). Patients with an IDH1-mutation with MPN-AP (10-19%) blasts are eligible for this study
Iadademstat concomitant medication considerations: Patients are not allowed to receive prophylactic hematopoietic colony stimulating factors, any complementary or alternative medicine \[any of various systems of healing or treating disease (as non-prescription supplements, herbal medicine and homeopathy)\]. Of note, patients may receive granulocyte colony-stimulating factor for management of febrile neutropenia or for prolonged neutropenia
Patients may not receive administration of live or live-attenuated vaccines. Administration of non-live vaccines included ribonucleic acid (RNA)-based vaccines is allowed and is recommended for pneumococcal, coronavirus, and influenza vaccines
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant women are excluded from this study because iadademstat is an LSD1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iadademstat, breastfeeding should be discontinued if the mother is treated with iadademstat. These potential risks also apply to the ASTX727 (35 mg decitabine + 100 mg cedazuridine) used in this study
Patients who require treatment while on study with concomitant drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline) except for drugs that are considered absolutely essential for the care of the patient and with appropriate treatment monitoring

Study Design

Enrollment

78 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (ASTX727)

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.

experimental: Arm II (ASTX727, iadademstat)

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.

Interventions

Biospecimen Collection

Undergo buccal swab and blood sample collection

Bone Marrow Aspiration

Undergo bone marrow aspiration and biopsy

Bone Marrow Biopsy

Undergo bone marrow aspiration and biopsy

Decitabine and Cedazuridine

Given PO

Iadademstat

Given PO

Primary outcome measure

Acute leukemia response-complete (ALR-C) rate [ Time Frame: Within 4 cycles (cycle length = 28 days) ]

Central Contacts and Locations

Locations

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Kiran Naqvi

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Kiran Naqvi

Stanford Cancer Institute Palo Alto

Recruiting

Palo Alto, California, United States, 94304

Contacts

Site Public Contact

650-498-7061 cancertrialsinfo@stanford.edu

Principal Investigator:

Gabriel N. Mannis

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Site Public Contact

916-734-3089

Principal Investigator:

Francisco A. Socola

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

UM Sylvester Comprehensive Cancer Center at Coral Springs

Recruiting

Coral Springs, Florida, United States, 33065

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

UM Sylvester Comprehensive Cancer Center at Doral

Recruiting

Doral, Florida, United States, 33166

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Terrence J. Bradley

UM Sylvester Comprehensive Cancer Center at Hollywood

Recruiting

Hollywood, Florida, United States, 33021

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

UM Sylvester Comprehensive Cancer Center at Kendall

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

Recruiting

North Miami, Florida, United States, 33181

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Terrence J. Bradley

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Terrence J. Bradley

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Contacts

Site Public Contact

800-679-0775 ClinicalTrials@moffitt.org

Principal Investigator:

Andrew T. Kuykendall

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Anand A. Patel

UC Comprehensive Cancer Center at Silver Cross

Recruiting

New Lenox, Illinois, United States, 60451

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Anand A. Patel

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Anand A. Patel

UChicago Medicine Northwest Indiana

Recruiting

Crown Point, Indiana, United States, 46307

Contacts

Site Public Contact

855-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Anand A. Patel

University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Abdulraheem M. Yacoub

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Abdulraheem M. Yacoub

University of Kansas Hospital-Indian Creek Campus

Recruiting

Overland Park, Kansas, United States, 66211

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Abdulraheem M. Yacoub

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Abdulraheem M. Yacoub

NYP/Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-746-1848

Principal Investigator:

Ghaith Abu Zeinah

Carolinas Medical Center/Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28203

Contacts

Site Public Contact

800-804-9376

Principal Investigator:

Brittany K. Ragon

Atrium Health Cabarrus/LCI-Concord

Recruiting

Concord, North Carolina, United States, 28025

Contacts

Site Public Contact

800-804-9376

Principal Investigator:

Brittany K. Ragon

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066 Jamesline@osumc.edu

Principal Investigator:

Andrew Srisuwananukorn

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777 ou-clinical-trials@ouhsc.edu

Principal Investigator:

Zimu Gong

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97239

Contacts

Site Public Contact

503-494-1080 trials@ohsu.edu

Principal Investigator:

Jessica M. Stempel

Vanderbilt University/Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Site Public Contact

800-811-8480

Principal Investigator:

Ashwin Kishtagari

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100 cancerinfo@hci.utah.edu

Principal Investigator:

Ami Patel

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430 CTOclinops@vcu.edu

Principal Investigator:

Thuy Ho

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-01.