Acute Myeloid LeukemiaPhase 1NCT07617363
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
A Phase 1 study testing ATRN-119 and Decitabine in people with Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This single-center, open-label, phase I study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antileukemic activity of ATRN-119 (mosipasertib) alone and in combination with decitabine in patients with TP53-mutated AML or higher-risk myelodysplastic syndrome (HR-MDS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
- What is being tested?
- ATRN-119 and Decitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2026to 30 Nov 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Diagnosis of AML or higher-risk MDS (HR-MDS) according to the World Health Organization (WHO) 5th Edition or International Consensus Classification (ICC) 2022 criteria.
- HR-MDS is defined as:
- IPSS-R (score > 3.5) or IPSS-M (score > 0.5) OR
- ≥ 10% bone marrow blasts
- At least one of the following demonstrated on standard of care testing:
- A pathogenic or likely pathogenic TP53 mutation with a VAF ≥10%
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- A TP53 or chromosome 17p deletion detected in ≥10% of cells by a cytogenetic assay
- >20% p53-positive cells by immunohistochemistry
- Meeting R/R disease criteria for AML or HR-MDS:
- Patients with R/R AML must have received at least 1 prior AML-directed treatment regimen appropriate for their disease and fitness. Patients with FLT3, IDH1, IDH2, or NPM1 mutations must also have previously received, or been deemed ineligible for, an approved targeted therapy directed against the relevant mutation. In addition, patients must meet at least one of the following criteria:
- Disease progression during treatment with, or failure to achieve CR, CRh, or CRi after ≥ 2 cycles of a hypomethylating agent (HMA) plus venetoclax.
- Disease progression during treatment with, or failure to achieve CR, CRh, or CRi after ≥ 4 cycles of HMA-based therapy when venetoclax was contraindicated, not tolerated, or otherwise considered clinically inappropriate.
- First relapse with an initial remission duration < 12 months
- First relapse following failed salvage chemotherapy
- Relapse after allogeneic hematopoietic cell transplant
- Second or subsequent relapse
- Patients with R/R HR-MDS must have received at least 1 prior MDS-directed treatment regimen appropriate for their disease and fitness. Patients with IDH1 mutations must also have previously received, or been deemed ineligible for, an approved targeted therapy directed against the relevant mutation. Patients must meet at least one of the following criteria:
- Disease progression during treatment with, or failure to achieve CR, CRh, or CRi after ≥ 4 cycles of HMA-based therapy or 2 cycles of HMA in combination with another agent, including an investigational agent as part of a clinical trial or in routine clinical care.
- Relapse after allogeneic hematopoietic cell transplant
- Second or subsequent relapse
- At least 18 years of age.
- ECOG performance status ≤ 2
- Adequate organ function within 28 days prior to the first dose of mosipasertib as defined below:
- Total bilirubin ≤ 2.0 x IULN; patients with known or suspected Gilbert's syndrome may have total bilirubin ≤ 3 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Creatinine clearance ≥ 45 mL/min/1.73 m^2 by Cockcroft-Gault formula
- The effects of mosipasertib and decitabine on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after the last dose of mosipasertib or decitabine on study (whichever is later) for people of childbearing potential and 3 monthsafter the last dose of mosipasertib or decitabine on study (whichever is later) for people able to father a child.
- Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Who cannot join
- Active CNS involvement by AML requiring therapeutic intervention.
- Active graft-versus-host disease (GVHD) requiring systemic immunosuppressive therapy except for low-dose steroids (prednisone ≤ 10 mg per day or other steroid equivalent)
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
- Currently receiving any other investigational agents.
- Concomitant systemic treatment with inhibitors of BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, or MATE2-K. Patients may be eligible after a washout period of at least 7 days or 5 half-lives, whichever is longer, prior to the first dose of ATRN-119.
- Concomitant systemic treatment with strong inhibitors or inducers of CYP enzymes. Patients may be eligible after a washout period of 5 half-lives or 14 days (whichever is longer) before PK Run-In Day 1 or C1D1 (whichever is applicable) for strong inducers, and 5 half-lives or 7 days (whichever is longer) before PK Run-In Day 1 or C1D1 (whichever is applicable) for strong inhibitors.
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- A history of allergic reactions attributed to or known hypersensitivity to compounds of similar chemical or biologic composition to mosipasertib, decitabine, or other agents used in the study.
- Persistent corrected QT interval using Fridericia's formula (QTcF) >480 msec (CTCAE v6.0 ≥ grade 2), except in patients with bundle branch block and/or ventricular paced rhythm for whom QTc cannot be reliably assessed using standard correction methods.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, clinically significant autoimmune disease requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, or clinically significant or uncontrolled cardiac arrhythmia. Patients with a 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 Function Classification; to be eligible for this trial, patients should be a class 2B or better.
- Conditions that may impair oral drug administration or absorption, including inability to swallow oral medications, malabsorption syndromes, or other clinically significant gastrointestinal disorders.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of PK Run-In Day 1/Cycle 1 Day 1.
- HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing is not required in the absence of known history of infection.
- Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load by PCR on suppressive therapy are eligible. HBV testing is not required in the absence of known history of infection.
- History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing is not required in the absence of known history of infection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
Geoffrey L Uy, MD, 314-747-2449, agasanli@wustl.edu
Geoffrey L Uy, MD
About this study
Official title: A Phase I Study of ATRN-119, an ATR Inhibitor, in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
This single-center, open-label, phase I study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antileukemic activity of ATRN-119 (mosipasertib) alone and in combination with decitabine in patients with TP53-mutated AML or higher-risk myelodysplastic syndrome (HR-MDS). The primary objective is to identify the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE) of ATRN-119 (mosipasertib) plus decitabine. The study is based on the hypothesis that ATR inhibition with ATRN-119 (mosipasertib) will enhance sensitivity to decitabine in TP53-mutated disease, resulting in deeper and more durable clinical responses.
- Being tested
- ATRN-119, Decitabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATRN-119Drug
Also called Mosipasertib
Provided in 50 mg and 100 mg capsules or 50 mg and 250 mg tablets and are administered by mouth.
DecitabineDrug
Also called Dacogen
Decitabine is provided as a 50 mg injection in a single-dose vial.
| Study group | Role | What they receive |
|---|---|---|
| Part A Dose Escalation Dose Level 1: ATRN-119 | Experimental | * Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 of each 28-day cycle.
* Patients in Part A may (but are not required to) transition to the current dose level being evaluated in Part B (and thus receive decitabine concurrently with mosipasertib) following completion of the Cycle 1 DLT evaluation period for all patients in their assigned dose level, provided that dose level is determined to be safe. In order to transition from Part A to Part B, a patient must have persistent AML or HR-MDS (meaning they must NOT have achieved a CR without MRD) and must meet all eligibility criteria. In addition, both they and their physician must be in agreement that the decision to transition is desired and acceptable.
* Patients may continue treatment for up to 24 total cycles across Parts A and B unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. Receives: Drug: ATRN-119 |
| Part A Dose Escalation Dose Level 2: ATRN-119 | Experimental | * Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 of each 28-day cycle.
* Patients in Part A may (but are not required to) transition to the current dose level being evaluated in Part B (and thus receive decitabine concurrently with mosipasertib) following completion of the Cycle 1 DLT evaluation period for all patients in their assigned dose level, provided that dose level is determined to be safe. In order to transition from Part A to Part B, a patient must have persistent AML or HR-MDS (meaning they must NOT have achieved a CR without MRD) and must meet all eligibility criteria. In addition, both they and their physician must be in agreement that the decision to transition is desired and acceptable.
* Patients may continue treatment for up to 24 total cycles across Parts A and B unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. Receives: Drug: ATRN-119 |
| Part A Dose Escalation Dose Level 3: ATRN-119 | Experimental | * Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 of each 28-day cycle.
* Patients in Part A may (but are not required to) transition to the current dose level being evaluated in Part B (and thus receive decitabine concurrently with mosipasertib) following completion of the Cycle 1 DLT evaluation period for all patients in their assigned dose level, provided that dose level is determined to be safe. In order to transition from Part A to Part B, a patient must have persistent AML or HR-MDS (meaning they must NOT have achieved a CR without MRD) and must meet all eligibility criteria. In addition, both they and their physician must be in agreement that the decision to transition is desired and acceptable.
* Patients may continue treatment for up to 24 total cycles across Parts A and B unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. Receives: Drug: ATRN-119 |
| Part B Dose Escalation Dose Level 1: ATRN-119 + Decitabine | Experimental | * Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 and 20 mg/m^2 of decitabine given intravenously (IV) on Days 1-5 of each 28-day cycle.
* Patients may continue treatment for up to 24 total cycles unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. Receives: Drug: ATRN-119; Drug: Decitabine |
| Part B Dose Escalation Dose Level 2: ATRN-119 + Decitabine | Experimental | * Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 and 20 mg/m^2 of decitabine given intravenously (IV) on Days 1-5 of each 28-day cycle.
* Patients may continue treatment for up to 24 total cycles unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. Receives: Drug: ATRN-119; Drug: Decitabine |
| Part B Dose Escalation Dose Level 3: ATRN-119 + Decitabine | Experimental | * Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 and 20 mg/m^2 of decitabine given intravenously (IV) on Days 1-5 of each 28-day cycle.
* Patients may continue treatment for up to 24 total cycles unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. Receives: Drug: ATRN-119; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and grade of treatment-emergent adverse events (TEAEs) as assessed via CTCAE v6.0 (All Patients)
Measured: From start of treatment until 30 days after last dose of ATRN-119 (approximately 23 months)
Incidence of dose-limiting toxicities (DLTs) during Cycle 1 as assessed via CTCAE v6.0 (All Patients)
The DLT evaluation period is 28 days from initiation of study treatment (Cycle 1), except in cases of persistent neutropenia meeting hematologic DLT criteria, for which the observation window will extend to 42 days from treatment initiation. DLTs are defined in the protocol.
Measured: From Cycle 1 Day 1 to end of Cycle 1 Day 28/Cycle 1 Day 42 (total time 28-42 days)
Secondary outcomes (15)
Rate of Complete Remission (CR) (All Patients)
European LeukemiaNet (ELN) 2022 Response Criteria assesses AML and the International Working Group (IWG) 2023 Response Criteria assesses Higher-Risk MDS (HR-MDS).
CR AML: Bone marrow blasts < 5%; absence of circulating blasts; absence of extramedullary disease; ANC ≥ 1.0 x 10^9/L (1,000/μL); platelet count ≥ 100 x 10^9/L (100,000/μL).
CR HR-MDS: Bone marrow: < 5% myeloblasts; dysplasia may persist and peripheral blood: hemoglobin ≥ 10 g/dL, platelets ≥ 100 x 10^9/L, neutrophils ≥ 1.0 x 10^9/L, blasts 0%
Measured: Through completion of treatment (estimated total time 22 months)
Rate of Complete Remission with partial hematologic recovery (CRh) (All Patients)
European LeukemiaNet (ELN) 2022 Response Criteria assesses AML and the International Working Group (IWG) 2023 Response Criteria assesses Higher-Risk MDS (HR-MDS).
CRh is defined according to the ELN 2022 Response Criteria: ANC ≥ 0.5 x 10^9/L (500 μL) and platelet count ≥ 50 x 10^9/L (50,000/μL), otherwise all other CR criteria met
CRh is defined according to the IWG 2023 Response Criteria: Bone marrow: < 5% myeloblasts; dysplasia may persist; Peripheral blood: not meeting criteria for CR or CRL; no hemoglobin threshold required, platelets ≥ 50 x 10^9/L, neutrophils ≥ 0.5 x 10^9/L, blasts 0%
Measured: Through completion of treatment (estimated total time 22 months)
Rate of Partial Remission (PR) (All Patients)
European LeukemiaNet (ELN) 2022 Response Criteria assesses AML and the International Working Group (IWG) 2023 Response Criteria assesses Higher-Risk MDS (HR-MDS).
PR is defined according to the ELN 2022 Response Criteria: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pre-treatment bone marrow blast percentage by at least 50%
PR is defined according to the IWG 2023 Response Criteria: All CR criteria except: Bone marrow blasts decreased by ≥ 50% over pretreatment but still ≥ 5% and Cellularity and morphology not relevant
Measured: Through completion of treatment (estimated total time 22 months)
Duration of Response (DoR) (All Patients)
DoR will be measured from the first documented response until earliest date of disease progression or death from any cause, as defined in the protocol or disease-specific criteria (ELN 2022 for AML and IWG 2023 for HR-MDS). DOR will be summarized among responders only. Individuals who do not exhibit any disease progression or death during the follow-up period are censored at the last date of the response assessment.
Measured: From first documented response until disease progression or death (up to 48 months)
Event-free Survival (EFS) (All Patients)
EFS will be measured from Cycle 1 Day 1 to treatment failure, relapse after response, progression, or death from any cause, consistent with protocol definitions and disease-specific response criteria (ELN 2022 for AML and IWG 2023 for HR-MDS). EFS will be summarized in the efficacy-evaluable population. Participants without an event will be censored at the last disease assessment date at which they were known to be event-free.
Measured: From Cycle 1 Day 1 to treatment failure, relapse after response, progression, or death (up to 48 months)
Overall Survival (OS) (All Patients)
OS will be measured from Cycle 1 Day 1 to death from any cause. Participants alive at last follow-up will be censored on the date last known alive. OS will be summarized in all treated participants.
Measured: From Cycle 1 Day 1 to death from any cause (up to 48 months)
Rate of Complete Remission with incomplete count recovery (CRi) (AML Patients only)
Response is assessed according to the ELN 2022 Response Criteria for AML.
CRi is defined as all CR criteria except for residual neutropenia < 1.0 x 10^9/L (500/μL) or thrombocytopenia < 100 x 10^9/L (50,000/μL); CRi should only include patients not meeting the definition of CRh.
Measured: Through completion of treatment (estimated total time 22 months)
Rate of morphologic leukemia-free state (MLFS) (AML Patients only)
Response is assessed according to the ELN 2022 Response Criteria for AML.
MLFS is defined as bone marrow blasts < 5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery required.
Measured: Through completion of treatment (estimated total time 22 months)
Rate of composite Complete Remission (cCR) (AML Patients only)
Response is assessed according to the ELN 2022 Response Criteria for AML.
cCR is defined as complete remission (CR) + complete remission with partial hematologic recovery (CRh) + complete remission with incomplete hematologic recovery (CRi)
Measured: Through completion of treatment (estimated total time 22 months)
Overall Response Rate (ORR) (AML Patients only)
Response is assessed according to the ELN 2022 Response Criteria for AML. ORR is defined as complete remission (CR) + complete remission with partial hematologic recovery (CRh) + complete remission with incomplete hematologic recovery (CRi) + partial remission (PR) + morphologic leukemia-free state (MLFS)
Measured: Through completion of treatment (estimated total time 22 months)
Rate of Complete Remission (CR) equivalent (HR-MDS patients only)
CR is assessed according to the IWG 2023 Response Criteria for HR-MDS.
CR: Bone marrow: < 5% myeloblasts; dysplasia may persist; Peripheral blood: hemoglobin ≥ 10 g/dL, platelets ≥ 100 x 10^9/L, neutrophils ≥ 1.0 x 10^9/L, blasts 0%
Measured: Through completion of treatment (estimated total time 22 months)
Rate of Complete Remission with limited count recovery (CRL) (HR-MDS patients only)
CRL is assessed according to the IWG 2023 Response Criteria for HR-MDS.
CRL (CRuni and CRbi): Bone marrow: < 5% myeloblasts; dysplasia may persist; Peripheral blood: blasts 0%; Complete remission unilineage (CRuni): peripheral blood not meeting CR but only one of the following: hemoglobin ≥ 10 g/dL, platelets ≥ 100 x 10^9/L, neutrophils ≥ 1.0 x 10^9/L Complete remission bilineage (CRbi): peripheral blood not meeting CR but only two of the following: hemoglobin ≥ 10 g/dL, platelets ≥ 100 x 10^9/L, neutrophils ≥ 1.0 x 10^9/L
Measured: Through completion of treatment (estimated total time 22 months)
Rate of Hematological Improvement (HI) (HR-MDS patients only)
HI is assessed according to the IWG 2018 Response Criteria for HR-MDS.
HI: Not meeting criteria for complete remission (CR) (or CR equivalent) or complete remission unilineage (CRuni) or complete remission with limited count recovery (CRL); HIerythroid (HI-E); HIplatelets (HI-P); HIneutrophils (HI-N).
Measured: Through completion of treatment (estimated total time 22 months)
Rate of composite Complete Remission (cCR) (HR-MDS patients only)
cCR is assessed according to the IWG 2023 Response Criteria for HR-MDS.
cCR is defined as complete remission (CR) + complete remission (CR) equivalent + complete remission with limited count recover (CRL) + complete remission with partial hematologic recovery (CRh)
Measured: Through completion of treatment (estimated total time 22 months)
Overall Response Rate (ORR) (HR-MDS patients only)
Response is assessed via the IWG 2023 Response Criteria for HR-MDS. ORR is defined as complete remission (CR) + complete remission (CR) equivalent + complete remission with limited count recover (CRL) + complete remission with partial hematologic recovery (CRh) + partial remission (PR) + hematological improvement (HI)
Measured: Through completion of treatment (estimated total time 22 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2026
- Study start30 Nov 2026 (estimated)
- Primary completion31 Oct 2029 (estimated)
- Study completion30 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Enrollment will begin with Dose Level 1 in Part A. Once the prespecified safety evaluations have been concluded for that dose level, and provided that dose level is determined to be safe, enrollment to Dose Level 1 in Part B will open, as will enrollment to Dose Level 2 in Part A; when enrollment to both Parts A and B is open simultaneously, allocation of individual patients will occur at the discretion of the PI.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Aprea Therapeutics, National Cancer Institute (NCI), The V Foundation for Cancer Research
- Responsible party
- Sponsor
- Investigators
- Geoffrey L Uy, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07617363
- Sponsor's protocol ID
- 202609141
- Other IDs
- P50CA171963
- Status last verified
- Nov 2026
- First submitted
- 20 May 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported in publications arising from this study will be made available to qualified investigators.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of ATRN-119, an ATR Inhibitor, in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
- ClinicalTrials.gov ID
- NCT07617363
- Acronym / sponsor ID
- 202609141
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Aprea Therapeutics, National Cancer Institute (NCI), The V Foundation for Cancer Research
- Study start
- 30 Nov 2026 (estimated)
- Primary completion
- 31 Oct 2029 (estimated)
- Study completion
- 30 Nov 2031 (estimated)
- First posted
- 1 Jun 2026 (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.
This single-center, open-label, phase I study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antileukemic activity of ATRN-119 (mosipasertib) alone and in combination with decitabine in patients with TP53-mutated AML or higher-risk myelodysplastic syndrome (HR-MDS). The primary objective is to identify the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE) of ATRN-119 (mosipasertib) plus decitabine. The study is based on the hypothesis that ATR inhibition with ATRN-119 (mosipasertib) will enhance sensitivity to decitabine in TP53-mutated disease, resulting in deeper and more durable clinical responses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Enrollment will begin with Dose Level 1 in Part A. Once the prespecified safety evaluations have been concluded for that dose level, and provided that dose level is determined to be safe, enrollment to Dose Level 1 in Part B will open, as will enrollment to Dose Level 2 in Part A; when enrollment to both Parts A and B is open simultaneously, allocation of individual patients will occur at the discretion of the PI.
| Arm | Type | Receives |
|---|---|---|
| Part A Dose Escalation Dose Level 1: ATRN-119 | Experimental | Drug: ATRN-119* Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 of each 28-day cycle. * Patients in Part A may (but are not required to) transition to the current dose level being evaluated in Part B (and thus receive decitabine concurrently with mosipasertib) following completion of the Cycle 1 DLT evaluation period for all patients in their assigned dose level, provided that dose level is determined to be safe. In order to transition from Part A to Part B, a patient must have persistent AML or HR-MDS (meaning they must NOT have achieved a CR without MRD) and must meet all eligibility criteria. In addition, both they and their physician must be in agreement that the decision to transition is desired and acceptable. * Patients may continue treatment for up to 24 total cycles across Parts A and B unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. |
| Part A Dose Escalation Dose Level 2: ATRN-119 | Experimental | Drug: ATRN-119* Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 of each 28-day cycle. * Patients in Part A may (but are not required to) transition to the current dose level being evaluated in Part B (and thus receive decitabine concurrently with mosipasertib) following completion of the Cycle 1 DLT evaluation period for all patients in their assigned dose level, provided that dose level is determined to be safe. In order to transition from Part A to Part B, a patient must have persistent AML or HR-MDS (meaning they must NOT have achieved a CR without MRD) and must meet all eligibility criteria. In addition, both they and their physician must be in agreement that the decision to transition is desired and acceptable. * Patients may continue treatment for up to 24 total cycles across Parts A and B unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. |
| Part A Dose Escalation Dose Level 3: ATRN-119 | Experimental | Drug: ATRN-119* Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 of each 28-day cycle. * Patients in Part A may (but are not required to) transition to the current dose level being evaluated in Part B (and thus receive decitabine concurrently with mosipasertib) following completion of the Cycle 1 DLT evaluation period for all patients in their assigned dose level, provided that dose level is determined to be safe. In order to transition from Part A to Part B, a patient must have persistent AML or HR-MDS (meaning they must NOT have achieved a CR without MRD) and must meet all eligibility criteria. In addition, both they and their physician must be in agreement that the decision to transition is desired and acceptable. * Patients may continue treatment for up to 24 total cycles across Parts A and B unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. |
| Part B Dose Escalation Dose Level 1: ATRN-119 + Decitabine | Experimental | Drug: ATRN-119, Drug: Decitabine* Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 and 20 mg/m^2 of decitabine given intravenously (IV) on Days 1-5 of each 28-day cycle. * Patients may continue treatment for up to 24 total cycles unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. |
| Part B Dose Escalation Dose Level 2: ATRN-119 + Decitabine | Experimental | Drug: ATRN-119, Drug: Decitabine* Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 and 20 mg/m^2 of decitabine given intravenously (IV) on Days 1-5 of each 28-day cycle. * Patients may continue treatment for up to 24 total cycles unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. |
| Part B Dose Escalation Dose Level 3: ATRN-119 + Decitabine | Experimental | Drug: ATRN-119, Drug: Decitabine* Patients will take ATRN-119 at the assigned dose level by mouth once per day on Days 1-28 and 20 mg/m^2 of decitabine given intravenously (IV) on Days 1-5 of each 28-day cycle. * Patients may continue treatment for up to 24 total cycles unless disease is considered refractory after Cycle 4, or until disease progression, unacceptable toxicity, or withdrawal, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Diagnosis of AML or higher-risk MDS (HR-MDS) according to the World Health Organization (WHO) 5th Edition or International Consensus Classification (ICC) 2022 criteria.
- At least one of the following demonstrated on standard of care testing:
- Meeting R/R disease criteria for AML or HR-MDS:
- At least 18 years of age.
- ECOG performance status ≤ 2
Key exclusion criteria (14 listed)
- Active CNS involvement by AML requiring therapeutic intervention.
- Active graft-versus-host disease (GVHD) requiring systemic immunosuppressive therapy except for low-dose steroids (prednisone ≤ 10 mg per day or other steroid equivalent)
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
- Currently receiving any other investigational agents.
- Concomitant systemic treatment with inhibitors of BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, or MATE2-K. Patients may be eligible after a washout period of at least 7 days or 5 half-lives, whichever is longer, prior to the first dose of ATRN-119.
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 |
|---|---|---|
| ATRN-119Also: MosipasertibProvided in 50 mg and 100 mg capsules or 50 mg and 250 mg tablets and are administered by mouth. | Drug | Part A Dose Escalation Dose Level 1: ATRN-119, Part A Dose Escalation Dose Level 2: ATRN-119, Part A Dose Escalation Dose Level 3: ATRN-119, Part B Dose Escalation Dose Level 1: ATRN-119 + Decitabine, Part B Dose Escalation Dose Level 2: ATRN-119 + Decitabine, Part B Dose Escalation Dose Level 3: ATRN-119 + Decitabine |
| DecitabineAlso: DacogenDecitabine is provided as a 50 mg injection in a single-dose vial. | Drug | Part B Dose Escalation Dose Level 1: ATRN-119 + Decitabine, Part B Dose Escalation Dose Level 2: ATRN-119 + Decitabine, Part B Dose Escalation Dose Level 3: ATRN-119 + Decitabine |
Primary outcome
Number and grade of treatment-emergent adverse events (TEAEs) as assessed via CTCAE v6.0 (All Patients)
Time frame: From start of treatment until 30 days after last dose of ATRN-119 (approximately 23 months)
Incidence of dose-limiting toxicities (DLTs) during Cycle 1 as assessed via CTCAE v6.0 (All Patients)
Time frame: From Cycle 1 Day 1 to end of Cycle 1 Day 28/Cycle 1 Day 42 (total time 28-42 days)
The DLT evaluation period is 28 days from initiation of study treatment (Cycle 1), except in cases of persistent neutropenia meeting hematologic DLT criteria, for which the observation window will extend to 42 days from treatment initiation. DLTs are defined in the protocol.
15 secondary outcomes
Rate of Complete Remission (CR) (All Patients)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of Complete Remission with partial hematologic recovery (CRh) (All Patients)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of Partial Remission (PR) (All Patients)
Time frame: Through completion of treatment (estimated total time 22 months)
Duration of Response (DoR) (All Patients)
Time frame: From first documented response until disease progression or death (up to 48 months)
Event-free Survival (EFS) (All Patients)
Time frame: From Cycle 1 Day 1 to treatment failure, relapse after response, progression, or death (up to 48 months)
Overall Survival (OS) (All Patients)
Time frame: From Cycle 1 Day 1 to death from any cause (up to 48 months)
Rate of Complete Remission with incomplete count recovery (CRi) (AML Patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of morphologic leukemia-free state (MLFS) (AML Patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of composite Complete Remission (cCR) (AML Patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Overall Response Rate (ORR) (AML Patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of Complete Remission (CR) equivalent (HR-MDS patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of Complete Remission with limited count recovery (CRL) (HR-MDS patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of Hematological Improvement (HI) (HR-MDS patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Rate of composite Complete Remission (cCR) (HR-MDS patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Overall Response Rate (ORR) (HR-MDS patients only)
Time frame: Through completion of treatment (estimated total time 22 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported in publications arising from this study will be made available to qualified investigators.
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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.
Geoffrey L Uy, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ATRN-119 and Decitabine in people with Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome, run by Washington University School of Medicine 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 28 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: opening soon, as of the sponsor's last update on 6 Nov 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Geoffrey L Uy, MD (314-747-2449, agasanli@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and grade of treatment-emergent adverse events (TEAEs) as assessed via CTCAE v6.0 (All Patients) (time frame: From start of treatment until 30 days after last dose of ATRN-119 (approximately 23 months)). The study lists 2 primary outcomes in all. 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 6 Nov 2026; AzTrials last refreshed its copy on 7 Nov 2026.