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Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms | Clinical Trials | Clareo Health

WITHDRAWNPHASE1/PHASE2

Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms

NCT06284460•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

The goal of Part 1 of this clinical research study is to find the highest tolerable dose of ASTX029 that can be given in combination with ASTX727 to participants who have RAS-mutant MDS or MDS/MPN. The goal of Part 2 of this clinical research study is to learn if the dose of ASTX029 found in Part 1 can help to control the disease when used in combination with ASTX727.

Detailed Description

Primary Objectives: * Phase 1 dose escalation: to determine safety, tolerability and MTD of ASTX029 in RAS mutant MDS, CMML and other MDS/MPN * Phase 2 dose expansion: to determine the safety, tolerability and overall response rate (ORR) of ASTX727 in combination with ASTX029 in RAS mutant MDS, CMML and other MDS/MPN * Incidence of AEs, MTD and changes in clinical laboratory values. * Measures of efficacy: overall response rate (ORR) defined as sum of CR + complete cytogenetic remission + partial remission + marrow response + clinical benefit for MDS/MPN and defined as CR + mCR + PR + HI in MDS Secondary Objectives: * To determine other efficacy outcomes such as duration of response, leukemia-free survival (LFS), progression-free survival (PFS) and overall survival (OS). * To evaluate differences in response and efficacy outcomes by MDS/MPN IWG response criteria based on disease subtypes and genomic features. * Correlative studies * To evaluate changes in clonal composition and VAF of identified mutations with therapy. * To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ASTX029 and the combination of ASTX727 with ASTX029 in patients with RAS mutant MDS, CMML and other MDS/MPN

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Age ≥ 18 years as MDS and MDS/MPN are a very rare disease in the pediatric setting.
•Diagnosis of MDS or MDS/MPN (including CMML, aCML, MDS/MPN-U) according to WHO and:
•* Initial phase 1 cohorts (cohorts A): MDS participants with no response after 4 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 or relapse or progression after any number of cycles OR MDS/MPN relapsed/refractory following treatment with hydroxyurea OR at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with hydroxiurea.
•* Phase 2 dose expansion cohort:
•* Relapsed MDS cohort (Cohort B): no response after 4 cycles of azacitidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles.
•* Relapsed MDS/MPN cohort (Cohort C): relapsed/refractory following treatment with hydroxyurea or at least 4 cycles of azacytidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles or who are intolerant of treatment with wih hydroxiurea.
•Known mutation in genes leading to RAS pathway activation (NRAS, KRAS, BRAF, CBL, NF1, PTPN11).
•Creatinine clearance ≥30ml/min based on the Cockcroft-Gault Glomerular Filtration Rate estimation.
•Adequate hepatic function with total bilirubin ≤1.5x ULN, AST or ALT ≤3 xULN.
•ECOG Performance Status 0-2.
+11 more criteria

Exclusion Criteria

•Participants who are currently receiving treatment for a malignancy (not including basal cell carcinoma, nonmelanoma skin cancer, cervical carcinoma in situ, early stage breast cancer or localized prostate cancer treated with hormone therapy). Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit or not requiring active treatment at the time of enrollment.
•Participants who are receiving any other investigational agents.
•Participants who have an active, life-threatening, or clinically-significant uncontrolled systemic infection requiring hospitalization.
•Participants who have a known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy).
•Pregnant women are excluded from this study because ASTX029 and ASTX727 are agents 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 these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study.
•Participants with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine devices \[IUD\], double-barrier method \[spermicidal jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) throughout the study.
•Female participants with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
•Participants receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy within 7 days of therapy initiation.
•Participants known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months).
•Participants with history of HIV with CD4+ T-cell (CD4+) counts \<350 cell/mcL or with AIDS-defining opportunistic infections in the last 12 months are also excluded. Participants with well controlled HIV (defined as CD4+ counts \>350 cells/mcL with undetectable viral load prior to enrollment with no AIDS-defining opportunistic infections in the past 12 months) on therapy with antiretroviral therapies known to be metabolites of cytochrome P450 (CYP3A4) enzymes will also be excluded.
+4 more criteria

Locations (1)

MD Anderson Cancer Cente

Houston, Texas, United States

Key Dates

Start Date

January 31, 2025

Primary Completion Date

December 1, 2025

Completion Date

December 1, 2027

Last Updated

February 13, 2026

Conditions

Pathway Mutant Myelodysplastic SyndromesMyelodysplastic NeoplasmMyeloproliferative Neoplasm

Interventions

ASTX029

DRUG

ASTX727

DRUG

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AML (Acute Myelogenous Leukemia)Acute Lymphoid Leukemia (ALL)+9 more

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RECRUITINGPHASE1/PHASE2

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 13, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms

Inclusion Criteria

Exclusion Criteria

A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia

Phase Ib Study of CD33 FPBMC in Patients With MRD+ AML or MDS

Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia or Myelodysplastic Syndrome (MDS)

An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms

Evaluation of the Pathobiology of CALR-mutated MPN Cells