Deoxycytidine + Deoxythymidine for Telomere Biology Disorder

Overseen By Mike Lorrey-Parena, BSN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Suneet Agarwal

Must not be taking: Androgens, Growth factors

Disqualifiers: Severe aplastic anemia, Chronic diarrhea, Kidney disease, High-risk myelodysplastic syndrome, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking medications intended to improve blood cell production, like androgens or growth factors, at least 30 days before joining. Other medications that could interfere with the study may also need to be stopped, as determined by the study doctor.

What data supports the effectiveness of the drug Deoxycytidine for Telomere Biology Disorder?

Research shows that 5-aza-2'-deoxycytidine, a form of deoxycytidine, is effective in treating myelodysplastic syndromes, with a 54% response rate in elderly patients, suggesting potential benefits for other conditions involving cell growth and stability. ^{1 2 3 4 5}

Is Deoxycytidine + Deoxythymidine safe for humans?

There is no specific safety data available for Deoxycytidine + Deoxythymidine in humans, but research suggests that thymidine (a component of the treatment) can influence telomere length, which is important for cell health and stability. ^{6 7 8 9 10}

How does the drug Deoxycytidine + Deoxythymidine differ from other treatments for telomere biology disorders?

This drug is unique because it targets telomere length by supplementing with deoxythymidine, which has been shown to promote telomere elongation and enhance telomerase activity, potentially offering a new approach to treating telomere biology disorders where telomere maintenance is crucial. ^{8 11 12 13 14}

What is the purpose of this trial?

The goal of this clinical trial is to learn if a combination therapy of deoxycytidine (dC) plus deoxythymidine (dT) is safe in patients with telomere biology disorders. The main questions it aims to answer are: * Is the therapy safe with tolerable side effects in patients with telomere biology disorders? * Are peripheral blood counts improved in patients with telomere biology disorders who have cytopenias? Participants will: * Take study drug by mouth three times daily for 24 weeks * Make approximately 2 visits to Boston Children's Hospital during the 24 weeks: once at the beginning of treatment and once at the end of treatment. * Go to a lab for a blood draw an additional 6 times during treatment. * Have 9 phone calls with a research nurse, including one 4 weeks after treatment ends. * Keep a diary to track doses of study drug that were taken or missed.

Research Team

Helen Reed, MD, MPH

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for patients with telomere biology disorders, specifically those who have low blood counts (cytopenias). Participants must be able to take oral medication three times daily, visit Boston Children's Hospital twice, go for additional blood draws six times, and maintain communication with a research nurse.

Inclusion Criteria

I can consume liquids by mouth or through a feeding tube.

Participants must exhibit at least one clinical manifestation associated with a telomere biology disorder, in the judgment of the PI

I am older than 1 year and 60 years old or younger.

Exclusion Criteria

I do not have high-risk blood disorders or any other active cancer.

Participants must not be on other medications or study agents or have other uncontrolled intercurrent illness that could interfere with study interpretation, in the opinion of the study Principal Investigator (PI)

Participants must not have psychological or social conditions that would limit adherence with study requirements, in the opinion of the study PI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enteral nucleoside therapy with dose escalation for 24 weeks

24 weeks

2 visits (in-person), 6 lab visits, 9 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 phone call

Treatment Details

Interventions

• Deoxycytidine
• Deoxythymidine

Trial Overview The trial is testing the safety of a combination therapy using deoxycytidine (dC) and deoxythymidine (dT) in patients with telomere biology disorders. It aims to see if this treatment can improve blood counts over a period of 24 weeks with regular monitoring.

Participant Groups

Group I: dC/dT Experimental Treatment 2 Interventions

Participants will take study therapy three times daily over 24 weeks with dose escalation.

Who Is Running the Clinical Trial?

Suneet Agarwal

Lead Sponsor

Trials

1

Recruited

40+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Exposure to hypomethylating 5-aza-2'-deoxycytidine (decitabine) causes rapid, severe DNA damage, telomere elongation and mitotic dysfunction in human WIL2-NS cells. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The effect in vitro of 2'-deoxycytidine on the metabolism and cytotoxicity of 2',3'-dideoxycytidine. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Interaction of deoxycytidine and deoxycytidine analogs in normal and leukemic human myeloid progenitor cells. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Telomere dysfunction induced by chemotherapeutic agents and radiation in normal human cells. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Thymidine nucleotide metabolism controls human telomere length. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Replication Stress and Telomere Dysfunction Are Present in Cultured Human Embryonic Stem Cells. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Novel screen for anti-cancer drugs that elevate chromosome instability (CIN) using human artificial chromosome (HAC). [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Telomere neurobiology. [2008]

12. Canada pubmed.ncbi.nlm.nih.gov

Recognition and elongation of telomeres by telomerase. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

The RNA component of human telomerase. [2023]

14. Japan pubmed.ncbi.nlm.nih.gov

Telomeres and telomerase in human hematologic neoplasia. [2019]