Evaluation of the Efficacy of Hypomethylating Agent Versus Standard Intensive Chemotherapy Induction Based on 5hmC - a Novel, Blood Epigenetic Marker for Assessing Measurable Residual Disease in Patients With Acute Myeloid Leukemia
The Methodist Hospital Research Institute
Summary
This is a therapeutic intervention trial evaluating the clinical utility of a novel blood-based epigenetic biomarker-genome-wide 5-hydroxymethylcytosine (5hmC) in cell-free DNA (cfDNA)-for assessing measurable residual disease (MRD) in patients with newly diagnosed acute myeloid leukemia (AML). The study compares the efficacy of hypomethylating agent (HMA)-based therapy versus intensive induction chemotherapy, using the 5hmC biomarker to guide post-induction treatment decisions. Approximately 112 adult patients will be enrolled and assigned to treatment arms based on a stratified sampling scheme. Blood samples will be collected at defined intervals to assess MRD status. Primary endpoints include minimal residual disease (MRD) negativity rate, duration of remission, event-free survival (EFS), and overall survival (OS).
Description
This is a therapeutic intervention trial evaluating the efficacy of a novel, blood epigenetic marker \[genome-wide 5 hydroxymethylcytosine (5hmC) of cell free DNA (cfDNA)\] for assessing measurable residual disease (MRD) in patients with acute myeloid leukemia (AML). Using the highly sensitive cfDNA 5hmC method, the trial will evaluate clinical efficacy of induction therapy and minimal residual disease (MRD) guided therapy in AML patients. Female or male patients aged 18 years, or older, with newly diagnosed de novo AML who will receive induction therapy with either hypomethylating agent (HMA)…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial. Spanish speaking patients will be included and translation services will be provided as needed. 2. Male or female, 18 years of age or older, on the day of informed consent signing. 3. Newly diagnosed de novo AML 5\. Expected life expectancy of at least 6 months 6. Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits and examinations. 7. Women with childbearing potential and men should…
Interventions
- Diagnostic Test5hmC Biomarker
The 5hmC marker will be used to determine treatment modality post-induction therapy. After Week 4 of standard-of-care therapy (either HMA-based treatment or intensive induction chemotherapy), 5hmC biomarker testing will be performed. If MRD is positive, patients will continue the same standard-of-care treatment or crossover to the other arm of the study. If MRD is negative, patients will proceed with consolidation (either HSCT or continue on same treatment). For patients receiving HMA-based treatment, blood samples will be collected ± 5 days before and after 4 and 12 weeks of therapy. For patients receiving intensive chemotherapy blood samples will be collected ± 5 days before and after 4 and 12 weeks of therapy.
- DrugVenetoclax
Venetoclax is a BCL-2 inhibitor FDA Approved for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, decitabine or low-dose cytarabine.
- DrugDecitabine 20 mg/m²/day for 5 days
Decitabine is a nucleoside metabolic inhibitor that is administered as an intravenous infusion over a 1-3 hours.
- DrugAzacitidine (AZA)
Azacitidine can be given as a sub-cutaneous injection or intravenously.
Location
- Houston Methodist Neal Cancer CenterHouston, Texas