RECRUITING

Nucleoside Therapy in Patients With Telomere Biology Disorders

Conditions

Telomere Biology Disorders Dyskeratosis Congenita Revesz Syndrome Hoyeraal Hreidarsson Syndrome Telomere Biology Disorders With Bone Marrow Failure Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)Pulmonary Fibrosis, Familial (Telomere Biology Disorder)nucleoside phase I deoxycytidine deoxythymidine safety tolerability pharmacokinetics telomere lengths bone marrow clonal hematopoiesis bone marrow failure pulmonary fibrosis

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 problems with the bone marrow or blood or lungs changed after 6 months of dC+dT treatment in patients with telomere biology disorders? 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.

Official Title

Nucleoside Therapy in Patients With Telomere Biology Disorders

Quick Facts

Study Start:2025-09

Study Completion:2029-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06817590

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 70 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥ 1 year and ≤ 70 years * Karnofsky performance status ≥ 50 for participants ≥16 years of age and Lansky performance status ≥ 50 for participants \<16 years of age * Diagnosis requirement. Participants must meet at least one of the following requirements for a diagnosis of a telomere biology disorder: 1. Age-adjusted mean telomere length \< 1%ile in peripheral blood lymphocytes by flow cytometry-fluorescence in situ hybridization (flow-FISH), as reported by a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory 2. Pathogenic or likely pathogenic variant(s) in one of the follow telomere biology associated genes: DKC1, TERC, TERT, NOP10, NHP2, WRAP53/TCAB1, TINF2, CTC1, RTEL1, ACD, PARN, NAF1, STN1, ZCCHC8, POT1, RPA1, DCLRE1B, TYMS, as reported by a CLIA-approved laboratory. * Participants must exhibit at least one active clinical manifestation associated with a telomere biology disorder, in the judgment of the PI, which includes but is not limited to the following: one or more peripheral blood cytopenias, bone marrow hypocellular for age, pulmonary abnormalities, liver abnormalities, gastrointestinal bleeding, immunodeficiency or immune dysregulation, ophthalmologic abnormalities, or neurologic abnormalities. * Participants must be able to take enteral liquids by mouth or enteral feeding tube. * Female participants who are sexually active and could become pregnant must use two effective methods of contraception, at least one of which must be considered a highly effective method. * Participants (or parent/legally authorized representative for minors) must demonstrate the ability to understand and willingness to provide informed consent, which will be documented using an institutionally approved informed consent procedure.	* Participants must not have very severe aplastic anemia necessitating bone marrow transplant at the time of enrollment. Very severe aplastic anemia is defined by the presence of at least 2 of the following: ANC \<200 cells/microliter, platelets \<20,000 cells/microliter, absolute reticulocyte count \<40,000 cells/microliter. If individuals with very severe aplastic anemia are not expected to undergo bone marrow transplant either due to the lack of an acceptable donor or medical co-morbidities and otherwise meet the inclusion/exclusion criteria, then they would be eligible for enrollment in this trial. * Participants must not otherwise be expected to undergo bone marrow transplantation within 6 months of enrollment. * Participants must not be taking concurrent medications intended to improve hematopoiesis such as androgens or growth factors, including granulocyte colony stimulating factor, erythropoietin, or thrombopoietin mimetics. If any of these therapies were taken previously, patients must wait 30 days after cessation of the therapy before enrollment on this trial. * Participants must not have chronic diarrhea or an average baseline stool output of more than 4 stools per day. * Participants must not have gastrointestinal disorders that may impair enteral absorption of dC/dT, such as inflammatory bowel disease or short bowel syndrome. * Participants must not have chronic kidney disease with an estimated glomerular filtration rate \< 60 mL/min/1.73 m2. * 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 high-risk myelodysplastic syndrome or leukemia or other active malignancy. * Pregnant individuals will not be eligible for enrollment given the physiological changes in blood counts that occur during pregnancy. * Breastfeeding mothers will not be eligible for enrollment due to the unknown risk to nursing infants.

Inclusion Criteria

Exclusion Criteria

* Age ≥ 1 year and ≤ 70 years
* Karnofsky performance status ≥ 50 for participants ≥16 years of age and Lansky performance status ≥ 50 for participants \<16 years of age
* Diagnosis requirement. Participants must meet at least one of the following requirements for a diagnosis of a telomere biology disorder:
1. Age-adjusted mean telomere length \< 1%ile in peripheral blood lymphocytes by flow cytometry-fluorescence in situ hybridization (flow-FISH), as reported by a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory
2. Pathogenic or likely pathogenic variant(s) in one of the follow telomere biology associated genes: DKC1, TERC, TERT, NOP10, NHP2, WRAP53/TCAB1, TINF2, CTC1, RTEL1, ACD, PARN, NAF1, STN1, ZCCHC8, POT1, RPA1, DCLRE1B, TYMS, as reported by a CLIA-approved laboratory.
* Participants must exhibit at least one active clinical manifestation associated with a telomere biology disorder, in the judgment of the PI, which includes but is not limited to the following: one or more peripheral blood cytopenias, bone marrow hypocellular for age, pulmonary abnormalities, liver abnormalities, gastrointestinal bleeding, immunodeficiency or immune dysregulation, ophthalmologic abnormalities, or neurologic abnormalities.
* Participants must be able to take enteral liquids by mouth or enteral feeding tube.
* Female participants who are sexually active and could become pregnant must use two effective methods of contraception, at least one of which must be considered a highly effective method.
* Participants (or parent/legally authorized representative for minors) must demonstrate the ability to understand and willingness to provide informed consent, which will be documented using an institutionally approved informed consent procedure.

* Participants must not have very severe aplastic anemia necessitating bone marrow transplant at the time of enrollment. Very severe aplastic anemia is defined by the presence of at least 2 of the following: ANC \<200 cells/microliter, platelets \<20,000 cells/microliter, absolute reticulocyte count \<40,000 cells/microliter. If individuals with very severe aplastic anemia are not expected to undergo bone marrow transplant either due to the lack of an acceptable donor or medical co-morbidities and otherwise meet the inclusion/exclusion criteria, then they would be eligible for enrollment in this trial.
* Participants must not otherwise be expected to undergo bone marrow transplantation within 6 months of enrollment.
* Participants must not be taking concurrent medications intended to improve hematopoiesis such as androgens or growth factors, including granulocyte colony stimulating factor, erythropoietin, or thrombopoietin mimetics. If any of these therapies were taken previously, patients must wait 30 days after cessation of the therapy before enrollment on this trial.
* Participants must not have chronic diarrhea or an average baseline stool output of more than 4 stools per day.
* Participants must not have gastrointestinal disorders that may impair enteral absorption of dC/dT, such as inflammatory bowel disease or short bowel syndrome.
* Participants must not have chronic kidney disease with an estimated glomerular filtration rate \< 60 mL/min/1.73 m2.
* 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 high-risk myelodysplastic syndrome or leukemia or other active malignancy.
* Pregnant individuals will not be eligible for enrollment given the physiological changes in blood counts that occur during pregnancy.
* Breastfeeding mothers will not be eligible for enrollment due to the unknown risk to nursing infants.

Contacts and Locations

Study Contact

Helen Reed, MD, MPH

CONTACT

617-355-1454

helen.reed@childrens.harvard.edu

Mike Lorrey-Parena, BSN

CONTACT

857-218-4269

michael.lorrey-parena@childrens.harvard.edu

Principal Investigator

Helen Reed, MD, MPH

PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Study Locations (Sites)

Boston Childrens Hospital

Boston, Massachusetts, 02115

United States

Collaborators and Investigators

Sponsor: Suneet Agarwal

Helen Reed, MD, MPH, PRINCIPAL_INVESTIGATOR, Boston Children's Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-09

Study Completion Date2029-06

Study Record Updates

Study Start Date2025-09

Study Completion Date2029-06

Terms related to this study

Keywords Provided by Researchers

nucleoside
phase I
deoxycytidine
deoxythymidine
telomere biology disorders
safety
tolerability
pharmacokinetics
telomere lengths
bone marrow
clonal hematopoiesis
bone marrow failure
pulmonary fibrosis

Additional Relevant MeSH Terms

Telomere Biology Disorders
Dyskeratosis Congenita
Revesz Syndrome
Hoyeraal Hreidarsson Syndrome
Telomere Biology Disorders With Bone Marrow Failure
Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)
Pulmonary Fibrosis, Familial (Telomere Biology Disorder)