Pathway Mutant Myelodysplastic SyndromesPhase 1/2NCT06284460
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
A Phase 1/2 study testing ASTX029 and ASTX727 in people with Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pathway Mutant Myelodysplastic Syndromes, Myelodysplastic Neoplasm, Myeloproliferative Neoplasm
- What is being tested?
- ASTX029 and ASTX727
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2025to 1 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Participant (or patient's legally authorized representative) must have signed an informed consent document indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study. Non-English speaking participants may be consented.
- Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to cycle 1 day 1 of therapy.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Participants 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. The effects of ASTX029 on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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 prior to the study, for the duration of study participation, and 4 months after completion of ASTX727 and ASTX029 administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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.
- Participants with QTc interval >480 msec based on average of triplicate ECG readings at the Screening Visit using the Fridericia formula (QTcF), with the exception of participants with right bundle branch block or left bundle branch block.
- New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <50 by echocardiogram or multigated acquisition (MUGA) scan.
- History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.
- Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Conditions
- Pathway Mutant Myelodysplastic Syndromes, Myelodysplastic Neoplasm, Myeloproliferative Neoplasm
- Being tested
- ASTX029, ASTX727
- Medical subject headings
- Anemia, Refractory, with Excess of Blasts, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX029Drug
Given by PO
ASTX727Drug
Also called Inqovi
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Single agent ASTX029 | Experimental | Participants will take ASTX029 daily on days 1-21 of each 28-day cycle. ASTX029 should be taken with water on an empty stomach, no food 2 hours before and 2 hours after dose. Receives: Drug: ASTX029 |
| Cohorts B and C: Combination of ASTX727 + ASTX029 | Experimental | Participants will take ASTX029 daily on days 1-21 of each 28-day cycle. ASTX727 daily on days 1-5 of each 28-day cycle. Both ASTX029 and ASTX727 should be taken with water on an empty stomach, no food 2 hours before and 2 hours after dose. Receives: Drug: ASTX029; Drug: ASTX727 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start31 Jan 2025 (estimated)
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2027 (estimated)
Why it stopped: Drug Source Request
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pathway Mutant Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guillermo Montalban Bravo, Principal investigator, MD Anderson Cancer Cente
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06284460
- Sponsor's protocol ID
- 2022-0622
- Other IDs
- NCI-2024-01692
- Status last verified
- Feb 2026
- First submitted
- 21 Feb 2024
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06284460
- Acronym / sponsor ID
- 2022-0622
- Conditions
- Pathway Mutant Myelodysplastic Syndromes, Myelodysplastic Neoplasm, Myeloproliferative Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Drug Source Request
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 31 Jan 2025 (estimated)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 29 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Single agent ASTX029 | Experimental | Drug: ASTX029Participants will take ASTX029 daily on days 1-21 of each 28-day cycle. ASTX029 should be taken with water on an empty stomach, no food 2 hours before and 2 hours after dose. |
| Cohorts B and C: Combination of ASTX727 + ASTX029 | Experimental | Drug: ASTX029, Drug: ASTX727Participants will take ASTX029 daily on days 1-21 of each 28-day cycle. ASTX727 daily on days 1-5 of each 28-day cycle. Both ASTX029 and ASTX727 should be taken with water on an empty stomach, no food 2 hours before and 2 hours after dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASTX029Given by PO | Drug | Cohort A: Single agent ASTX029, Cohorts B and C: Combination of ASTX727 + ASTX029 |
| ASTX727Also: InqoviGiven by PO | Drug | Cohorts B and C: Combination of ASTX727 + ASTX029 |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guillermo Montalban Bravo principal investigator
MD Anderson Cancer Cente
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ASTX029 and ASTX727 in people with Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.