A Study of Oral Tetrahydrouridine-Decitabine in Relapsed or Refractory Myelodysplastic Syndromes (MDS)

Phase 1 Study of Oral Tetrahydrouridine-Decitabine to Treat Relapsed or Refractory Myelodysplastic Syndromes

The goal of this clinical trial is to learn about the safety and effectiveness of the combination drug Tetrahydrouridine (THU) and decitabine (DEC) to treat patients with relapsed or refractory myelodysplastic syndrome. The main questions it aims to answer are:

• Does the combination drug exhibit hematological and nonhematological toxicity?
• Does the combination drug improve health status and reduce the number of days of hospitalization?

Participants will:

• Take tetrahydrouridine and decitabine once a week for 24 weeks
• Visit the clinic once every 4 weeks for checkups and tests
• Keep a diary of their symptoms

Study Overview

• Status: Recruiting
• Conditions: MDS
• Intervention / Treatment: Drug: Decitabine

Detailed Description

This is a single-arm, open-label Phase 1 study of oral THU/decitabine to treat relapsed or refractory MDS. Patients will be treated for 24 weeks in the absence of clear evidence of progressive disease. The primary endpoint is safety. The secondary endpoints will include assessment of response rates by International Working Group (IWG) criteria, quality of life (QoL), and number of days of hospitalization. DNA-methyltransferase 1 (DNMT1) protein levels will be measured in bone marrow and peripheral blood white cells.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Davina Hoban; Phone Number: 201-618-4725; Email: dhoban@montefiore.org

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Einstein Medical Center
      • Principal Investigator: Mendel Goldfinger, MD
      • Contact: Davina Hoban; Phone Number: 201-618-4725; Email: dhoban@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have a diagnosis of MDS that has received one or more prior standard therapies and is relapsed or refractory
• Patients must be 18 years of age or older
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
• Patients must have adequate end-organ function
• Patient's body weight must be ≥ 41 kg
• Subjects must be able to understand and willing to sign a written informed consent document and complete study-related procedures.

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL)
• Prior treatment with ≥4 28-day cycles of parenteral or oral decitabine
• No other disease-directed therapy, save for hydroxyurea, including experimental or investigational drug therapy for 14 days prior to study entry (hydroxyurea should be discontinued ≥24 hours prior to initiation of study drug)
• Requiring concomitant treatment with drugs that are cytidine deaminase (CDA) substrates and/or inhibitors, e.g., cytarabine, 5-azacytidine, gemcitabine
• Currently pregnant or breastfeeding. Females of childbearing potential must have a negative serum pregnancy test within 72 hours of treatment start.
• Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates
• Women of Childbearing Potential (WOCBP) who are unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control; abstinence, condom) prior to study entry, for the duration of study participation, and until 6 months after taking the last dose of THU/decitabine
• Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a WOCBP, beginning at the screening visit and continuing until 6 months after taking the last dose of THU/decitabine
• 9. Patients with uncontrolled active human retrovirus (HIV) infection, as this will further increase the risk for opportunistic infections. However, patients with HIV with undetectable viral load by polymerase chain reaction (PCR), without opportunistic infection, and on a stable regimen of antiretroviral therapy are eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Oral capsules of THU followed 1 hour later by decitabine	Drug: Decitabine; Oral tetrahydrouridine and oral decitabine capsule; Other Names: Decagen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White blood cell measurement	Measure neutrophils count	every 4 weeks
Platelet count	Measure platelets in the blood	every 4 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response for high-risk MDS	Measure using International Working Group (IWG) 2023 response criteria	every 4 weeks
Hospitalization	Record the number of days of hospitalization	every 4 weeks

Collaborators and Investigators

• Sponsor: Treebough Therapies
• Collaborators: EpiDestiny, Inc.
• Investigators: Principal Investigator: Mendel Goldfinger, MD, Montefiore/Einstein Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: May 20, 2025
• First Submitted That Met QC Criteria: May 28, 2025
• First Posted (Actual): June 5, 2025

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Preleukemia; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine
• Other Study ID Numbers: 2024-00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No