ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS

NCT07617363 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 26-x191P50CA171963
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, phase I study with dose escalation and dose expansion testing the combination of ATRN-119 and decitabine in patients with TP53-mutated acute myeloid leukemia (AML) or higher-risk myelodysplastic syndrome (HR-MDS). The dose escalation phase will enroll patients with previously untreated, relapsed, or refractory AML or HR-MDS, regardless of TP53 alteration status, with the primary objective of determining safety and tolerability of ATRN-119 plus decitabine. The dose expansion phase will only enroll patients with previously untreated AML or HR-MDS with a TP53 alteration, with the primary objective of identifying the recommended phase 2 dose (RP2D).

Conditions

Acute Myeloid Leukemia; High-risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Number and grade of treatment-emergent adverse events (TEAEs) as assessed via CTCAE v6.0

  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

  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.

  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)

  Through completion of treatment (estimated total time 22 months)

• Rate of Complete Remission with partial hematologic recovery (CRh)

  Through completion of treatment (estimated total time 22 months)

• Rate of Partial Remission (PR)

  Through completion of treatment (estimated total time 22 months)

• Duration of Response (DoR)

  From first documented response until disease progression or death (up to 46 months)

• Event-free Survival (EFS)

  From Cycle 1 Day 1 to treatment failure, relapse after response, progression, or death (up to 46 months)

Study Arms (4)

Part A Dose Escalation Dose Level 1: ATRN-119 + Decitabine

EXPERIMENTAL

Patients will take 750 mg of ATRN-119 by mouth once per day on Days 1-28 of each 28-day cycle and 20 mg/m\^2 of decitabine given intravenously (IV) on Days 1-5. Patients may continue treatment for up to 24 cycles, or until disease progression, unacceptable toxicity, or withdrawal.

Drug: ATRN-119; Drug: Decitabine

Part A Dose Escalation Dose Level 2: ATRN-119 + Decitabine

EXPERIMENTAL

Patients will take 1000 mg of ATRN-119 by mouth once per day on Days 1-28 of each 28-day cycle and 20 mg/m\^2 of decitabine given intravenously (IV) on Days 1-5. Patients may continue treatment for up to 24 cycles, or until disease progression, unacceptable toxicity, or withdrawal.

Drug: ATRN-119; Drug: Decitabine

Part A Dose Escalation Dose Level -1: ATRN-119 + Decitabine

EXPERIMENTAL

Patients will take 500 mg of ATRN-119 by mouth once per day on Days 1-28 of each 28-day cycle and 20 mg/m\^2 of decitabine given intravenously (IV) on Days 1-5. Patients may continue treatment for up to 24 cycles, or until disease progression, unacceptable toxicity, or withdrawal.

Drug: ATRN-119; Drug: Decitabine

Part B Dose Expansion: ATRN-119 + Decitabine

EXPERIMENTAL

Patients will take the recommended phase 2 dose (RP2D) of ATRN-119 as determined in the dose escalation portion of the trial once per day on Days 1-28 of each 28-day cycle and 20mg/m\^2 of decitabine given intravenously (IV) on Days 1-5. Patients may continue treatment for up to 24 cycles, or until disease progression, unacceptable toxicity, or withdrawal.

Drug: ATRN-119; Drug: Decitabine

Interventions

ATRN-119 DRUG

ATRN-119 is provided in 50mg and 100mg capsules or 50mg and 250mg tablets and are administered by mouth.

Part A Dose Escalation Dose Level -1: ATRN-119 + Decitabine; Part A Dose Escalation Dose Level 1: ATRN-119 + Decitabine; Part A Dose Escalation Dose Level 2: ATRN-119 + Decitabine; Part B Dose Expansion: ATRN-119 + Decitabine

Decitabine DRUG

Decitabine is provided as a 50mg injection in a single-dose vial.

Also known as: Dacogen

Part A Dose Escalation Dose Level -1: ATRN-119 + Decitabine; Part A Dose Escalation Dose Level 1: ATRN-119 + Decitabine; Part A Dose Escalation Dose Level 2: ATRN-119 + Decitabine; Part B Dose Expansion: ATRN-119 + Decitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ii.≥ 10% bone marrow blasts
• Dose Escalation ONLY - One of the following:
• Previously untreated AML with ELN 2022 adverse-risk genetic features based on local testing, in patients who are ineligible for intensive induction chemotherapy (cytarabine plus an anthracycline) due to age, comorbidities, or performance status.
• Previously untreated HR-MDS
• Relapsed or refractory AML or HR-MDS meeting one or more of the following criteria: Failure to achieve CR, CRh, or CRi after ≥ 4 cycles of a hypomethylating agent (HMA); Failure to achieve CR, CRh, or CRi after ≥ 2 cycles of a HMA plus venetoclax; Overt disease progression during HMA-based therapy; 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
• Dose Expansion ONLY - Both of the following:
• AML or HR-MDS with a TP53 alteration, defined by the presence of any of the following features on local testing: Pathogenic or likely pathogenic TP53 mutation detected by molecular testing (with a minimum 2% VAF); Cytogenetic and/or FISH evidence of 17p deletion involving TP53 (with a minimum 2% cell involvement or the lower limit of detection of the assay); Increased hematopoietic p53 protein expression by immunohistochemistry (defined as \>20% p53-positive cells). Patients enrolled during the dose expansion phase on the basis of increased p53 protein expression who are subsequently found not to harbor a TP53 mutation on molecular testing may continue study treatment.
• No prior therapy for a myeloid neoplasm, with the exception of permitted treatments
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate organ function within 28 days prior to the first dose of ATRN-119 as defined below:
• Total bilirubin ≤ 2.0 x IULN; patients with known or suspected Gilbert's syndrome may have total bilirubin ≤ 5 mg/dL
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

You may not qualify if:

• Dose Expansion ONLY - Prior therapy for AML, HR-MDS, antecedent MDS, or antecedent myeloproliferative neoplasm (MPN) with the exception of erythropoiesis-stimulating agents, hematopoietic growth factors (e.g., G-CSF, thrombopoietin receptor agonists), hydroxyurea, luspatercept, imetelstat, all-trans retinoic acid (ATRA), and leukapheresis.
• 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 strong inhibitors or inducers of CYP3A4. Patients may be eligible after a washout period of 5 half-lives or 28 days (whichever is shorter).
• A history of allergic reactions attributed to or known hypersensitivity to compounds of similar chemical or biologic composition to ATRN-119, decitabine, or other agents used in the study.
• 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 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.

Sponsors & Collaborators

• Aprea Therapeutics: collaborator
• National Cancer Institute (NCI): collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Geoffrey L Uy, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Geoffrey L Uy, MD

CONTACT

314-747-8519; guy@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: June 1, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): December 31, 2031
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will become available beginning 6 months after publication of the primary study results and will remain available for at least 5 years thereafter.
• Access Criteria: De-identified individual participant data will be made available upon reasonable request to the Principal Investigator following publication of the primary study results. Requests must include a scientifically sound proposal and may require execution of a data use agreement and approval by Washington University and other applicable oversight bodies.

Locations

US (1)