Actively Recruiting
Proof-Of-Concept Study of Metabolically Optimized, Non-Cytotoxic 5-Azacitidine and Decitabine Epigenetic Therapy for Myeloid Malignancies
Led by Benjamin Tomlinson · Updated on 2026-05-18
20
Participants Needed
1
Research Sites
56 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Myelodysplastic syndrome (MDS), also called bone marrow failure, is a condition where the bone marrow produces fewer blood cells due to abnormal cell development. This study evaluates a new approach to treating MDS by using an alternating low-dose schedule of two chemotherapy drugs, 5-azacitidine (5AZA) and decitabine (DEC), to overcome resistance that can occur when either drug is given alone. The study is an early phase 1 pilot trial focusing on this combined treatment for myeloid malignancies including MDS and related disorders. Participants will receive 5AZA and DEC in a weekly alternating schedule: 5AZA at 50 mg/m² on Day 1 and DEC at 5 mg/m² on Day 4 each week. The first 8 weeks serve as an induction phase, followed by a long-term treatment phase starting from week 9. Treatment will continue for at least 24 weeks unless the disease progresses. Those who respond to therapy may continue treatment until relapse or disease progression not responsive to dose escalation. During the trial, participants will be regularly monitored for response using criteria including complete or partial response and hematologic improvement. Safety will be assessed by tracking adverse events. The study also explores biological markers related to treatment response. Participants may remain in the study for up to 6 months after treatment to assess overall response, with some outcomes followed for up to 2 years. Careful evaluation of blood counts, disease status, and side effects will guide treatment continuation and study assessments.
CONDITIONS
Brief Title
5-Azacitidine and Decitabine Epigenetic Therapy for Myeloid Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participants must have MDS or MDS/myeloproliferative overlap disorder with potential sensitivity to hypomethylating agent therapy, supported by prior evidence of response
- Diagnoses include various WHO-classified subtypes of MDS and MDS/MPN crossover syndromes with limited extramedullary hematopoiesis and mild reticulin fibrosis
- Indication for hypomethylating agent therapy includes symptomatic anemia, low platelet counts, transfusion dependence, or low neutrophil counts
- Lower risk MDS participants must have failed or have contraindications to available effective therapies like lenalidomide or epoetin
- Performance status of 60% or greater by Karnofsky Performance Status
- Adequate liver function with AST and ALT less than 3 times upper limit of normal and bilirubin within 1.5 times upper limit unless due to certain conditions
- Ability and willingness to provide informed consent and complete study procedures
You will not qualify if you...
- Participants with high or very high risk MDS by IPSS-R or intermediate-2 or higher risk
- Prior treatment with azacitidine, decitabine, or investigational hypomethylating agents with similar mechanisms
- Use of other disease-directed therapy except hydroxyurea within 14 days before study
- Unresolved toxicity grade 2 or higher from prior therapies
- Currently pregnant or breastfeeding; females of childbearing potential must have a negative pregnancy test
- Uncontrolled illnesses limiting life expectancy or study completion, including active infections without controlled treatment, uncontrolled malignancy, severe heart failure, unstable angina, unstable arrhythmias, decompensated liver cirrhosis
- Psychiatric or social issues limiting compliance
- Unwillingness to use dual contraception for females and males of reproductive potential
- Known active HIV infection unless stable on treatment with undetectable viral load
- Allergy or hypersensitivity to azacitidine or decitabine components
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Minimum of 24 weeks, continuing until disease progression or relapse
Participants will receive 5-azacytidine weekly on Day 1 and decitabine weekly on Day 4. The first 8 weeks consist of an induction phase followed by a long-term treatment phase. Treatment continues for a minimum of 24 weeks unless there is evidence of disease progression. Participants with any response may continue treatment until relapse or progression not sensitive to dose escalation.
Weekly visits for treatment administration
Duration - Up to 6 months for response evaluation and up to 2 years for duration of response
Participants are monitored for safety and duration of response after treatment ends.
Visits as scheduled for safety and response monitoring
Trial Site Locations
Total: 1 location
1
Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Actively Recruiting
Research Team
B
Benjamin Tomlinson, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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