[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"hoyeraal-hreidarsson-syndrome\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:hoyeraal-hreidarsson-syndrome":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,60],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":33,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":48,"lastUpdatePostDateStruct":49,"startDateStruct":52,"completionDateStruct":54,"leadSponsor":56,"locationsCount":59},"100578922","phase-1-nucleoside-therapy-in-patients-with-telomere-biology-disorders-100578922",false,"NCT06817590","Nucleoside Therapy in Patients With Telomere Biology Disorders","Inclusion Criteria:\n\n* Age ≥ 1 year and ≤ 70 years\n* Karnofsky performance status ≥ 50 for participants ≥16 years of age and Lansky performance status ≥ 50 for participants \\\u003C16 years of age\n* Diagnosis requirement. Participants must meet at least one of the following requirements for a diagnosis of a telomere biology disorder:\n\n  1. Age-adjusted mean telomere length \\\u003C 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\n\n     OR\n  2. Pathogenic or likely pathogenic variant(s) in one of the follow telomere biology associated genes: DKC1, TERC, TERT, NOP10, NHP2, WRAP53\u002FTCAB1, TINF2, CTC1, RTEL1, ACD, PARN, NAF1, STN1, ZCCHC8, POT1, RPA1, DCLRE1B, TYMS, as reported by a CLIA-approved laboratory.\n* 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.\n* Participants must be able to take enteral liquids by mouth or enteral feeding tube.\n* 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.\n* Participants (or parent\u002Flegally 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.\n\nExclusion Criteria:\n\n* 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 \\\u003C200 cells\u002Fmicroliter, platelets \\\u003C20,000 cells\u002Fmicroliter, absolute reticulocyte count \\\u003C40,000 cells\u002Fmicroliter. 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\u002Fexclusion criteria, then they would be eligible for enrollment in this trial.\n* Participants must not otherwise be expected to undergo bone marrow transplantation within 6 months of enrollment.\n* 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.\n* Participants must not have chronic diarrhea or an average baseline stool output of more than 4 stools per day.\n* Participants must not have gastrointestinal disorders that may impair enteral absorption of dC\u002FdT, such as inflammatory bowel disease or short bowel syndrome.\n* Participants must not have chronic kidney disease with an estimated glomerular filtration rate \\\u003C 60 mL\u002Fmin\u002F1.73 m2.\n* 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)\n* Participants must not have high-risk myelodysplastic syndrome or leukemia or other active malignancy.\n* Pregnant individuals will not be eligible for enrollment given the physiological changes in blood counts that occur during pregnancy.\n* Breastfeeding mothers will not be eligible for enrollment due to the unknown risk to nursing infants.","ALL","1 Year","70 Years",{"count":19,"type":20},36,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","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:\n\n* Is the therapy safe with tolerable side effects in patients with telomere biology disorders?\n* Are problems with the bone marrow or blood or lungs changed after 6 months of dC+dT treatment in patients with telomere biology disorders?\n\nParticipants will:\n\n* Take study drug by mouth three times daily for 24 weeks\n* 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.\n* Go to a lab for a blood draw an additional 6 times during treatment.\n* Have 9 phone calls with a research nurse, including one 4 weeks after treatment ends.\n* Keep a diary to track doses of study drug that were taken or missed.",[26,27,28,29,30,31,32],"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)",[34,35,36,37,38,39,40,41,42,43,44,45,46],"nucleoside","phase I","deoxycytidine","deoxythymidine","telomere biology disorders","safety","tolerability","pharmacokinetics","telomere lengths","bone marrow","clonal hematopoiesis","bone marrow failure","pulmonary fibrosis","RECRUITING","2026-03-16",{"date":50,"type":51},"2026-03-18","ACTUAL",{"date":53,"type":51},"2025-09-29",{"date":55,"type":20},"2029-06",{"name":57,"class":58},"Suneet Agarwal","OTHER",1,{"id":61,"slug":62,"hasResults":11,"nctId":63,"briefTitle":64,"officialTitle":64,"acronym":4,"eligibilityCriteria":65,"healthyVolunteers":11,"sex":15,"minAge":66,"maxAge":67,"enrollmentInfo":68,"targetDuration":4,"studyType":21,"phases":70,"briefSummary":72,"conditions":73,"keywords":83,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":85,"lastUpdatePostDateStruct":86,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":59},"100380322","phase-2-regenerative-medicine-to-restore-hematopoiesis-and-immune-function-in-immunodeficiencies-and-inherited-bone-marrow-failures-100380322","NCT04232085","Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures","Inclusion Criteria\n\nCohort A:\n\nPrimary Immune Deficiencies with indication for HCT:\n\n* Chronic granulomatous disease (CGD)\n* Wiskott-Aldrich syndrome (WAS)\n* Hyper-IgM syndrome\n* Common variable immunodeficiency (CVID)\n* Leukocyte adhesion deficiency-1 (LAD-1)\n* Severe Combined Immunodeficiency (SCID)\n* CTLA-4 deficiency\n* CARD9 deficiency\n* DOCK8 deficiency\n\nImmune Dysregulatory Syndromes:\n\n* Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome\n* Hemophagocytic lymphohistiocytosis (HLH) or related disorder with indication for transplant\n* CAEBV: Patients with chronic EBV infection (CAEBV) with indication for BMT:\n\nInherited Bone marrow failure disorders\n\n* Congenital amegakaryocytic thrombocytopenia (CAMT)\n* Diamond Blackfan anemia (DBA)\n* Shwachman Diamond Syndrome (SDS)\n* Thrombocytopenia Absent Radii (TAR)\n* Glanzmans thrombasthenia (GT)\n* Kostmann syndrome\n* Other indications and\u002For other PID, IDS, and IBMFS diagnoses as deemed appropriate by the PI.\n\nCohort B: Short telomere syndrome\n\nCohort C: Confirmed diagnosis of Fanconi anemia or non-Fanconi DNA-dsb repair disorders\n\n* Fanconi anemia\n* Non-Fanconi DNA-dsb repair disorders\n* Cerunnos-XRCC4-like factor deficiency (XLF or NHEJ1)\n* DNA ligase IV deficiency (LIG4)\n* Nijmegen breakage syndrome (NBS)\n* Increased DNA breakage after exposure of patient cells to DNA cross-linking agents such as diepoxybutane or mitomycin C and germline mutation(s) in an identified Fanconi pathway gene.\n\nAvailable donor as follows:\n\n* Fully HLA matched sibling or other first-degree family member.\n* Fully HLA matched unrelated 10\u002F10 donor using high-resolution DNA-based typing at the following genetic loci: HLA-A, -B, -C, DRB1, and DQB1.\n* Mismatched unrelated donor at 8 or 9\u002F10 alleles, using high-resolution typing as above.\n* HLA-haploidentical family members of any degree who match at least one allele of each of the following genetic loci: HLA-A, -B, -C, DRB1, and DQB1. A minimum match of 5\u002F10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.\n* The patient and\u002For legal guardian must sign informed consent for BMT.\n* Patients with adequate organ function as measured by\n* Cardiac: Left ventricular ejection fraction (LVEF) at rest must be ≥ 35%. For patients aged \\\u003C13 years, shortening fraction (SF) \\> 25% by echocardiogram or LVEF by MUGA may be used.\n* Hepatic: Bilirubin ≤ 3.0 mg\u002FdL; and ALT, AST, and Alkaline Phosphatase \\\u003C 5 x ULN.\n* Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) \\> 40 mL\u002Fmin\u002F1.73m2.\n* Pulmonary: PFT with FEV1 and FVC \\>\u002F= 50% of normal and DLCO corrected for Hgb \\>\u002F= 40% of normal. Patients unable to undergo PFTs should have stable resp status with SaO2 \\>90% on a max of 2L\u002Fmin supplemental O2.\n* Karnofsky or Lansky performance status ≥70%\n* Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time, or agree to abstinence.\n\nExclusion criteria\n\n* Patients will not be excluded on the basis of sex, racial or ethnic background.\n* Positive leukocytotoxic crossmatch.\n* Prior allogeneic stem cell transplant.\n* Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment. The investigators recognize that patients with CAEBV may have ongoing EBV viremia at the time of initiating pre-transplant therapy, but other patients should have no uncontrolled bacterial, viral, or fungal infections.\n* Diagnosis of idiopathic aplastic anemia\n* Seropositivity for the human immunodeficiency virus (HIV)\n* Active Hepatitis B or C determined by serology and\u002For NAT\n* Female patients who are diagnosed as pregnant by beta bHCG testing (per institutional practice) or who are breast-feeding.\n* Active malignancy or within the timeframe for significant concern for relapse of prior malignancy\n* For Cohort B and C: liver biopsy (if performed, not required) with moderate-severe fibrosis\u002Fcirrhosis\n\nDonor Eligibility\n\n* Donor must be medically, socially, and psychologically fit to donate\n* Bone marrow is the preferred graft source, however, PBSCs may be requested. In particular, PBSCs may be preferred for patients with active viral reactivations and\u002For for patients who would benefit from a higher count in the graft. Cord blood is not permitted.\n* First-degree relatives should be tested for degree of HLA match, CMV serology, ABO type, and complete blood count (CBC). An unrelated donor search should be initiated at the time the patient is referred for BMT.\n* Age ≥5 years\n* Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).\n* Lack of recipient anti-donor HLA antibody in recipient\n* Note: In some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if found to be at a level well below that detectable by flow cytometry. This will be decided on a case-by-case basis by the PI and one of the immunogenetics directors.\n* In inherited disorders, family members must be tested for carrier and disease status of the underlying disorders. In the event that family members are unaffected carriers, eligibility as donors will be decided upon by the PI on a case-by-case basis\n* In the event that two or more eligible donors are identified, the donor will be selected per institutional standards. Suggested criteria include the following:\n* Related is preferred over unrelated.\n* The potential donor that is youngest in age is preferred.\n* For CMV seronegative patients, a CMV seronegative donor is preferred. For CMV seropositive patients, a CMV seropositive donor is preferred.\n* Red blood cell compatibility, in order of preference:\n* RBC cross match compatible Minor ABO incompatibility, Major ABO incompatibility\n* If the patient is male, male donors are preferred.","4 Months","50 Years",{"count":69,"type":20},27,[71],"PHASE2","Phase II prospective trial to assess the rates of donor engraftment using reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) and post-transplant cyclophosphamide (PTCy) for patients with primary immune deficiencies (PID), immune dysregulatory syndromes (IDS), inherited bone marrow failure syndromes (IBMFS), short telomere syndromes, Fanconi anemia, and non-Fanconi DNA double-strand break (DNA-dsb) repair disorder.",[74,75,76,77,78,79,80,27,81,82],"Primary Immune Deficiency Disorder","Immune Deficiency Disease","Bone Marrow Failure","Short Telomere Length","Fanconi Anemia","Non Fanconi DNA-DSB Repair Disorder","Hoyeraal-Hreidarsson Syndrome","Telomere Biology Disorder","Short Telomere Syndrome",[84],"Bone Marrow Transplantation","2025-11-21",{"date":87,"type":51},"2025-11-28",{"date":89,"type":51},"2020-02-12",{"date":91,"type":20},"2028-12-31",{"name":93,"class":58},"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins"]