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

ConditionsAcute Myeloid LeukemiaHigh-risk Myelodysplastic Syndrome
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

IPSS-R (score > 3.5) or IPSS-M (score > 0.5) OR ii.≥ 10% bone marrow blasts

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

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • ATRN-119

    Drug

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

  • Decitabine

    Drug

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

Treatment groups

27 Participants
are divided into 4 treatment groups
Group A: Part A Dose Escalation Dose Level 1: ATRN-119 + DecitabineExperimental treatment 2 interventions
Group B: Part A Dose Escalation Dose Level 2: ATRN-119 + DecitabineExperimental treatment 2 interventions
Group C: Part A Dose Escalation Dose Level -1: ATRN-119 + DecitabineExperimental treatment 2 interventions
Group D: Part B Dose Expansion: ATRN-119 + DecitabineExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
From start of treatment until 30 days after last dose of ATRN-119 (approximately 23 months)
2

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.

Time frame
From Cycle 1 Day 1 to end of Cycle 1 Day 28/Cycle 1 Day 42 (total time 28-42 days)

Secondary outcomes

1

Rate of Complete Remission (CR)

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%

Time frame
Through completion of treatment (estimated total time 22 months)
2

Rate of Complete Remission with partial hematologic recovery (CRh)

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%

Time frame
Through completion of treatment (estimated total time 22 months)
3

Rate of Partial Remission (PR)

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

Time frame
Through completion of treatment (estimated total time 22 months)
4

Duration of Response (DoR)

DoR will be measured from the first documented response until 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.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Washington University School of Medicine

Lead sponsor

Aprea Therapeutics

Collaborator

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov

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