ATRN-119 + Decitabine for Acute Myeloid Leukemia and Myelodysplastic Syndrome
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores a new treatment for individuals with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS), particularly those with a TP53 gene mutation. In its early stages (Phase 1), the study aims to determine the safety and tolerability of combining two drugs, ATRN-119 (an experimental treatment) and decitabine. Initially, the trial will test different doses to assess patient reactions, then concentrate on those with a specific genetic change in their AML or HR-MDS. Eligible participants include those diagnosed with AML or HR-MDS who have not responded to previous treatments or are newly diagnosed but unable to undergo intensive chemotherapy. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.
Do I need to stop my current medications for the trial?
The trial does not specify if you need to stop taking your current medications, but you cannot take strong inhibitors or inducers of CYP3A4 without a washout period (time without taking these medications) of 5 half-lives or 28 days, whichever is shorter.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that decitabine, one of the drugs in this trial, works well and is generally safe for older patients with acute myeloid leukemia (AML). Most patients using decitabine experience manageable side effects, indicating its safety for many people. However, less information exists about ATRN-119, the other drug in this trial, because this is an early-phase study. Researchers are still learning about its safety and tolerability. In these early trials, the main goal is to ensure the treatment does not cause serious harm. Although detailed data on ATRN-119 is not yet available, researchers are closely monitoring its combination with decitabine to ensure patient safety.12345
Why are researchers excited about this trial's treatments?
Researchers are excited about ATRN-119 combined with decitabine for treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) because it introduces a novel approach to therapy. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, ATRN-119 focuses on specific molecular pathways involved in the progression of these blood cancers. This targeted approach could potentially lead to more effective treatments with fewer side effects. Additionally, the combination with decitabine, a DNA methylation inhibitor, enhances the treatment's ability to disrupt cancer cell growth and survival. This dual-action strategy offers hope for improved outcomes in patients who may not respond well to existing therapies.
What evidence suggests that this trial's treatments could be effective for AML or HR-MDS?
Research has shown that decitabine effectively treats high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It improves patient response to treatment and can increase survival rates. One study demonstrated that combining decitabine with other drugs led to significantly better outcomes, including higher response and remission rates. In this trial, researchers are testing ATRN-119 in combination with decitabine to determine if it can enhance treatment effectiveness. The hypothesis is that ATRN-119 might help decitabine target cancer cells more effectively, particularly in patients with TP53 mutations.12467
Who Is on the Research Team?
Geoffrey L Uy, MD
Principal Investigator
Washington University School of Medicine
Are You a Good Fit for This Trial?
This trial is for adults with acute myeloid leukemia (AML) or higher-risk myelodysplastic syndrome (HR-MDS), especially those whose cancer cells have a TP53 mutation. It includes people who are newly diagnosed, have relapsed, or did not respond to previous treatments.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Dose Escalation
Participants receive ATRN-119 and decitabine to determine safety and tolerability
Dose Expansion
Participants receive the recommended phase 2 dose (RP2D) of ATRN-119 and decitabine
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- ATRN-119
- Decitabine
Trial Overview
The study tests the safety and best dose of ATRN-119 combined with decitabine in patients with AML or HR-MDS. All participants receive both drugs; there is no placebo group. The trial has two phases: one to find safe doses and another focused on patients with TP53 mutations.
How Is the Trial Designed?
6
Treatment groups
Experimental Treatment
* 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.
* 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.
* 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.
* 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.
* 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.
* 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.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Washington University School of Medicine
Lead Sponsor
Aprea Therapeutics
Industry Sponsor
National Cancer Institute (NCI)
Collaborator
The V Foundation for Cancer Research
Collaborator
Citations
ATRN-119 in Combination With Decitabine in Patients ...
This is a single-center, open-label, phase I study with dose escalation and dose expansion testing the combination of ATRN-119 and ...
2.
ctv.veeva.com
ctv.veeva.com/study/atrn-119-in-combination-with-decitabine-in-patients-with-tp53-mutated-aml-or-higher-risk-mdsATRN-119 in Combination With Decitabine in Patients With ...
This is a single-center, open-label, phase I study with dose testing the combination of ATRN-119 and decitabine in patients with TP53-mutated ...
Decitabine in patients with myelodysplastic syndromes - PMC
We found that the 5‐day 20‐mg/m2/day and 8‐day 12‐mg/m2/day decitabine regimens have similar efficacy and safety in patients with intermediate‐ or high‐risk MDS ...
venetoclax-treated patients with acute myeloid leukemia ...
In addition, we note that decitabine/venetoclax treatment was associated with more rapid and deeper molecular clearance versus single-agent ...
5.
onco-hema.healthbooktimes.org
onco-hema.healthbooktimes.org/article/141742-advances-in-the-treatment-of-higher-risk-mds-current-strategies-and-emerging-therapiesAdvances in the Treatment of Higher-Risk MDS
Patients with higher-risk MDS have a poorer prognosis, with up to 40% of them experiencing disease progression to AML within two years of diagnosis.
Efficacy and safety of decitabine in treatment of elderly ... - PMC
In conclusion, decitabine is an effective and well-tolerated therapeutic alternative with acceptable side effects in elderly AML patients. Keywords: acute ...
A Call for Changes in Drug Development in Higher-Risk MDS
They argue that patients with TP53-inactivated MDS and chronic myelomonocytic leukemia should be treated in dedicated clinical trials. Further, ...
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