A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs)
NCT ID: NCT06661915
Last Updated: 2025-12-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
62 participants
INTERVENTIONAL
2025-08-14
2027-12-31
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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
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.
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
Interventions
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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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
Exclusion Criteria
* 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 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Anand A Patel
Role: PRINCIPAL_INVESTIGATOR
City of Hope Comprehensive Cancer Center LAO
Locations
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UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, United States
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana, United States
University of Kansas Clinical Research Center
Fairway, Kansas, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2024-08860
Identifier Type: REGISTRY
Identifier Source: secondary_id
10675
Identifier Type: OTHER
Identifier Source: secondary_id
10675
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2024-08860
Identifier Type: -
Identifier Source: org_study_id