Tetrahydrouridine + Decitabine for Myelodysplastic Syndrome

Overseen By Davina Hoban

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: EpiDestiny, Inc.

Must not be taking: Cytidine deaminase inhibitors

Disqualifiers: Acute promyelocytic leukemia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for myelodysplastic syndrome (MDS), a condition where the bone marrow fails to produce enough healthy blood cells. The researchers aim to determine if the combination of tetrahydrouridine (THU) and decitabine (DEC, a chemotherapy drug) is safe and effective, particularly for patients who have not responded to other treatments. Participants will take these medicines weekly and attend monthly check-ins to monitor their health and any side effects. This trial may suit individuals with MDS who have tried standard treatments but still need help managing their condition. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other disease-directed therapy, except for hydroxyurea, at least 14 days before starting the study. Hydroxyurea should be stopped at least 24 hours before the study begins. If you are taking drugs that are cytidine deaminase substrates or inhibitors, you will also need to stop those.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous research has studied the combination of tetrahydrouridine (THU) and decitabine (DEC) for safety in treating myelodysplastic syndrome (MDS). Studies have shown that when decitabine is combined with cedazuridine, its safety profile is similar to when administered alone through an IV (intravenous). This suggests that oral administration of decitabine, as with THU, might be equally safe.

Since the current trial is in its early stages, it primarily aims to assess the safety of this new combination. Early trials focus on understanding potential side effects. Participants will be closely monitored to manage any reactions promptly. Those considering joining this trial can expect researchers to watch for potential side effects to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelodysplastic syndrome?

Unlike the standard treatments for Myelodysplastic Syndrome, which are often administered intravenously, this investigational treatment uses an oral capsule form of Tetrahydrouridine (THU) followed by decitabine. This new delivery method could make the treatment more convenient and accessible for patients. Researchers are also excited because the combination of THU with decitabine could enhance the effectiveness of decitabine by increasing its stability and absorption in the body. This approach aims to improve outcomes and potentially reduce side effects, setting it apart from current therapies.

What evidence suggests that this treatment might be an effective treatment for myelodysplastic syndrome?

Research has shown that decitabine can effectively treat myelodysplastic syndrome (MDS). In one study, patients taking decitabine lived an average of 10.1 months, compared to 8.5 months for those receiving the best supportive care. This suggests that decitabine may help patients with high-risk MDS live longer. In this trial, researchers are combining decitabine with another drug, tetrahydrouridine (THU), to enhance its effectiveness. This combination aims to improve health outcomes and reduce hospital stays for patients. Early results suggest this new approach could be a promising option for those with MDS that is difficult to treat or has recurred after treatment. ^{2 4 6 7 8}

Who Is on the Research Team?

Mendel Goldfinger, MD

Principal Investigator

Montefiore/Einstein Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with Myelodysplastic Syndromes (MDS) that have not responded to previous treatments. Participants will take a combination drug weekly and visit the clinic monthly for checkups over a 24-week period, while keeping track of their symptoms.

Inclusion Criteria

I am 18 years old or older.

I can take care of myself but can't do heavy physical work.

My MDS has not improved or has returned after treatment.

Exclusion Criteria

I have completed at least 4 cycles of decitabine treatment.

I have been diagnosed with acute promyelocytic leukemia.

I need treatment with specific drugs like cytarabine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take tetrahydrouridine and decitabine once a week for 24 weeks

24 weeks

6 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine

Trial Overview The study tests the safety and effectiveness of Tetrahydrouridine (THU) combined with Decitabine (DEC) in treating MDS. It aims to determine if this drug reduces toxicity and hospitalization days, and improves health status.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

Oral capsules of THU followed 1 hour later by decitabine

Who Is Running the Clinical Trial?

EpiDestiny, Inc.

Lead Sponsor

Trials

4

Recruited

90+

Citations

1. withpower.com withpower.com/trial/phase-1-mds-5-2025-b2ca5

Tetrahydrouridine + Decitabine for Myelodysplastic ... Trial Overview The study tests the safety and effectiveness of Tetrahydrouridine (THU) combined with Decitabine (DEC) in treating MDS. It aims to determine if ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12177969/

Advances and challenges in the treatment of myelodysplastic ... Allo-HSCT is the only curative option for HR-MDS [76]. Allo-HSCT induced a 50% 3-year OS rate in HMA-naïve patients, a significant improvement ...

3. onclive.com onclive.com/view/high-risk-mds-clinical-efficacy-data

High-Risk MDS: Clinical Efficacy Data In the decitabine study, however, the median survival for those who received decitabine was 10.1 months vs 8.5 months for those who got best ...

4. ctv.veeva.com ctv.veeva.com/study/a-study-of-oral-tetrahydrouridine-decitabine-in-relapsed-or-refractory-myelodysplastic-syndromes-md

A Study of Oral Tetrahydrouridine-Decitabine in Relapsed or ... The goal of this clinical trial is to learn about the safety and effectiveness of the combination drug Tetrahydrouridine (THU) and ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2020-1210

Full article: Role of Cedazuridine/Decitabine in the ... New drug approval for myelodysplastic syndrome and chronic myelomonocytic leukemia. INQOVI® is a fixed drug combination of oral cedazuridine (100 mg) and ...

6. trials-api.montefioreeinstein.org trials-api.montefioreeinstein.org/node/413396

A Study of Oral Tetrahydrouridine-Decitabine in Relapsed ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7414597/

Oral cedazuridine/decitabine for MDS and CMML: a phase ... Efficacy and safety from oral cedazuridine/decitabine were consistent with those from IV decitabine in MDS and CMML patients.

8. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30030-4/abstract

An oral fixed-dose combination of decitabine and ... ... combination of decitabine and cedazuridine ... Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.