Nucleoside Therapy in Patients With Telomere Biology Disorders
Trial Parameters
Brief Summary
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.
Eligibility Criteria
Inclusion 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 OR 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