[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100253594":3},{"organization":4,"armGroups":7,"interventions":39,"overallOfficials":62,"centralContacts":67,"locations":76,"responsibleParty":110,"collaborators":34,"id":112,"slug":113,"hasResults":114,"nctId":115,"briefTitle":116,"officialTitle":116,"acronym":34,"eligibilityCriteria":117,"healthyVolunteers":118,"sex":119,"minAge":120,"maxAge":121,"enrollmentInfo":122,"targetDuration":34,"studyType":125,"phases":126,"briefSummary":128,"conditions":129,"keywords":135,"overallStatus":79,"whyStopped":34,"lastUpdateSubmitDate":141,"lastUpdatePostDateStruct":142,"startDateStruct":145,"completionDateStruct":147,"leadSponsor":149,"locationsCount":150},{"fullName":5,"class":6},"National Institutes of Health Clinical Center (CC)","NIH",[8,16,21,26,30,35],{"label":9,"type":10,"description":11,"interventionNames":12},"1\u002F IOC Arm-Closed with amendment L (07\u002F05\u002F2019)","EXPERIMENTAL","Immunosuppression Only Conditioning Arm",[13,14,15],"Drug: Immunosuppression Only Conditioning -Closed with amendment L","Drug: GVHD Prophylaxis","Procedure: Allo BMT",{"label":17,"type":10,"description":18,"interventionNames":19},"2\u002F RIC Arm - Closed with Amendment L (07\u002F05\u002F2019)","Reduced Intensity Conditioning Arm",[20,14,15],"Drug: Reduced Intensity Conditioning",{"label":22,"type":10,"description":23,"interventionNames":24},"3\u002F MAC Arm-Closed with amendment L (07\u002F05\u002F2019)","Myeloablative Conditioning Arm",[25,14,15],"Drug: Myeloablative Conditioning-Closed with amendment L",{"label":27,"type":10,"description":28,"interventionNames":29},"4\u002F RIC-MMF Arm","Reduced Intensity Conditioning with MMF duration de-escalation design",[20,14,15],{"label":31,"type":32,"description":33,"interventionNames":34},"5\u002F Donor Arm","NO_INTERVENTION","Donor",null,{"label":36,"type":10,"description":37,"interventionNames":38},"6\u002F RIC-SHORT Arm","Reduced Intensity Conditioning with shortened duration and dose-reduced PTCy",[20,14,15],[40,45,49,53,57],{"type":41,"name":42,"description":43,"armGroupLabels":44,"otherNames":34},"DRUG","Immunosuppression Only Conditioning -Closed with amendment L","Pentostatin 4 mg\u002Fm2\u002Fday IV on days -9 and -5, cyclophosphamide 5 mg\u002Fkg orally daily on days -9 through -2 (Closed with amendment L)",[9],{"type":41,"name":46,"description":47,"armGroupLabels":48,"otherNames":34},"Reduced Intensity Conditioning","pentostatin 4 mg\u002Fm2\u002Fday IV on days -11 and -7, cyclophosphamide 3 mg\u002Fkg orally daily on days -11 through -4; busulfan IV, pharmokinetically dosed, on days -3 and -2.",[17,27,36],{"type":41,"name":50,"description":51,"armGroupLabels":52,"otherNames":34},"Myeloablative Conditioning-Closed with amendment L","Pentostatin 4 mg\u002Fm2\u002Fday IV on days -13 and -9, low-dose cyclophosphamide orally daily on days -13 through -6; busulfan IV, pharmokinetically dosed, on days -5, -4, -3, and -2. (Closed with amendment L)",[22],{"type":41,"name":54,"description":55,"armGroupLabels":56,"otherNames":34},"GVHD Prophylaxis","High-dose, post-transplantation cyclophosphamide (PTCy) 25-50 mg\u002Fkg on days +3 and +4, sirolimus 6 mg on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through 0, +18, +25, or +35 depending on treatment arm and cohort.",[9,17,22,27,36],{"type":58,"name":59,"description":60,"armGroupLabels":61,"otherNames":34},"PROCEDURE","Allo BMT","Allogeneic blood or marrow transplantation",[9,17,22,27,36],[63],{"name":64,"affiliation":65,"role":66},"Dimana Dimitrova, M.D.","National Cancer Institute (NCI)","PRINCIPAL_INVESTIGATOR",[68,73],{"name":69,"role":70,"phone":71,"phoneExt":34,"email":72},"Amy H Chai","CONTACT","(240) 858-3755","amy.chai@nih.gov",{"name":64,"role":70,"phone":74,"phoneExt":34,"email":75},"(240) 858-3647","dimana.dimitrova@nih.gov",[77,95],{"facility":78,"status":79,"city":80,"state":81,"zip":82,"country":83,"countryCode":84,"cosmosGeoPoint":85,"geoPoint":90,"contacts":91},"National Institutes of Health Clinical Center","RECRUITING","Bethesda","Maryland","20892","United States","US",{"type":86,"coordinates":87},"Point",[88,89],-77.10026,38.98067,{"lat":89,"lon":88},[92],{"name":93,"role":70,"phone":94,"phoneExt":34,"email":34},"For more information at the NIH Clinical Center contact National Cancer Institute Referral Office","888-624-1937",{"facility":96,"status":79,"city":97,"state":98,"zip":99,"country":83,"countryCode":84,"cosmosGeoPoint":100,"geoPoint":104,"contacts":105},"National Marrow Donor Program","Minneapolis","Minnesota","55413-1753",{"type":86,"coordinates":101},[102,103],-93.26384,44.97997,{"lat":103,"lon":102},[106],{"name":107,"role":70,"phone":108,"phoneExt":34,"email":109},"John Miller, M.D.","763-406-8566","jmiller@nmdp.org",{"type":111,"investigatorFullName":34,"investigatorTitle":34,"investigatorAffiliation":34,"oldNameTitle":34,"oldOrganization":34},"SPONSOR","100253594","phase-2-pilot-trial-of-allogeneic-blood-or-marrow-transplantation-for-primary-immunodeficiencies-100253594",false,"NCT02579967","Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies","* INCLUSION CRITERIA - RECIPIENT:\n* Patients age \\>= 4 through 75 years\n* PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below:\n\n  1. PID as defined by identified genetic defect or, in the absence of a PID-associated genetic mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible upon discussion with the PI\n\n     * Mutations should be confirmed in a CLIA-certified laboratory, if such testing is available.\n     * Patients without a mutation must be deemed eligible and appropriate for allo BMT by the PI. Some patients may meet the clinical history criteria listed below, but will not be eligible if it is thought that their clinical history is due to a condition apart from an immune defect. In addition, patients with a PID of mild severity, such as those with selective IgA deficiency, may meet at least two of the clinical history criteria, but may be deemed inappropriate for allo BMT by the PI if it is felt that the risks of the procedure outweigh the severity of the disease.\n  2. Clinical history of at least two of the following:\n\n     * Life-threatening, organ-threatening, or severely disfiguring infection\n     * Protracted or recurrent infections requiring unusually long or repeated courses of antibiotics\n     * Infection with an opportunistic organism\n     * Chronic elevation in the blood (\\>=2 documented elevations over a period of 6 months or longer) of a latent virus (EBV, CMV, HHV6, HHV8, etc.)\n     * Evidence of immune dysregulation, as manifested by autoimmune disease, atopy, hemophagocytic lymphohistiocytosis\u002Fmacrophage activation syndrome, granulomas, splenomegaly, or lymphadenopathy\n     * Patients with hemophagocytic lymphohistiocytosis or macrophage activation syndrome related to an underlying lymphoma with no other clinical history suggestive of a primary immunodeficiency will not be eligible\n     * Hypogammaglobulinemia, dysglobulinemia, or impaired response to vaccination\n     * Hematologic malignancy or lymphoproliferative disorder\n     * Tissue diagnosis should be confirmed by NCI Department of Pathology, if prior biopsies are available\n     * Virus-associated solid tumor malignancy or pre-cancerous lesion\n     * Tissue diagnosis should be confirmed by NCI Department of Pathology, if prior biopsies are available\n* Availability of at least one 7-8\u002F8 (9-10\u002F10) HLA-matched related (excluding an identical twin) or unrelated donor, or an HLA-haploidentical related donor\n* Consensus among the PI, key AIs, and consultants (as necessary) that correction of the patient s immune system through BMT has the potential to improve the patient s health, quality of life, and\u002For life expectancy, after taking into consideration the patient s existing non-hematopoietic, potentially irreversible organ dysfunction\n* Adequate end-organ function, as measured by:\n\n  * Left ventricular ejection fraction (LVEF) \\>= 40% by 2D echocardiogram (ECHO) or MUGA, or left ventricular shortening fraction \\>= 20% by ECHO for patients receiving RIC or RIC-MMF, or RIC-SHORT, or LVEF \\>= 30% if the patient has radiologic evidence of aortic, renal, or coronary artery vasculitis.\n  * Pulmonary function tests: DL(co) (corrected for hemoglobin) and FEV(1) \\>= 40% of predicted for the RIC, RIC-MMF, and RIC-SHORT arms; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation \\>92% on room air. Calculations will be based on the values reported in CRIS.\n  * Bilirubin \\\u003C= 3.0 mg\u002FdL (unless due to Gilbert s syndrome or hemolysis) for patients receiving RIC, RIC-MMF, RIC-SHORT; ALT and AST 10 x ULN for patients receiving RIC, RIC-MMF, RIC-SHORT. Patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC, RIC-MMF, or RIC-SHORT arms if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially reversible with bone marrow transplant.\n  * Estimated creatinine clearance of \\>= 40 mL\u002Fmin\u002F1.73 m\\^2, calculated using the Cockcroft-Gault equation for adults and Schwartz formula for pediatric patients, for patients with creatinine levels above the institutional upper limit of normal\n* Karnofsky or Lansky performance status of \\>=60% or ECOG performance status of 2 or less\n* Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document\n* Not pregnant or breastfeeding. As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-allo BMT. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately.\n* Disease status: Patients with malignancy are to be referred in remission for evaluation, except in cases of virus-associated malignancy who may be referred at any time. Should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to his\u002Fher primary hematologist-oncologist for treatment. If this course of action is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease under the current study, although this should only occur as a bridge to transplant. If under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he\u002Fshe must come off the study. Patients receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol.\n\nEXCLUSION CRITERIA - RECIPIENT:\n\n* Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection\u002Freactivation prior to allo BMT.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (cyclophosphamide, busulfan, pentostatin, sirolimus, MMF, filgrastim or filgrastim biosimilar) used in the study\n* Active psychiatric disorder which may compromise compliance with the transplant protocol, or which does not allow for appropriate informed consent\n* Active central nervous system (CNS) involvement by malignancy, except in cases of virus-associated malignancies with CNS involvement in which case the patient may benefit from the transplant to control the malignancy.\n* MAGT1 mutation and active need to take anti-platelet agents and\u002For therapeutic anti-coagulation that cannot be interrupted during aplasia.\n* HIV positive or other acquired immunodeficiency that, as determined by the PI, interferes with the assessment of PID severity and\u002For the attribution of clinical manifestations of immunodeficiency to a PID.\n* Lack of adequate central venous access potential\n\nInclusion Criteria (Related Donor):\n\n* Ages \\>= 4\n* Related donor deemed suitable and eligible and willing to donate per clinical evalations who are additionally willing to donate blood, urine, and marrow specimens for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors but is not required for clinical donation, so it is possible that not all related donors will enroll on this study.\n\nExclusion Criteria (Related Donor):\n\nNone\n\nINCLUSION CRITERIA - UNRELATED DONOR:\n\n* Ages \\>= 18\n* Unrelated donors will be evaluated in accordance with existing NMDP Standard Policies and Procedures, available at: http:\u002F\u002Fbethematch.org\u002FAbout-Us\u002FGlobal-transplant-network\u002FStandards\u002F, except for the additional requirement of EBV serostatus testing. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study.\n\nEXCLUSION CRITERIA - UNRELATED DONOR:\n\n-Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http:\u002F\u002Fbethematch.org\u002FAbout-Us\u002FGlobal-transplant-network\u002FStandards\u002F.",true,"ALL","4 Years","75 Years",{"count":123,"type":124},354,"ESTIMATED","INTERVENTIONAL",[127],"PHASE2","Background:\n\nAllogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems.\n\nObjective:\n\nTo see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies.\n\nEligibility:\n\nDonors: Healthy people ages 4 or older\n\nRecipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant\n\nDesign:\n\nParticipants will be screened with medical history, physical exam, and blood tests.\n\nParticipants will have urine tests, EKG, and chest x-ray.\n\nDonors will have:\n\nBone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone.\n\nOR\n\nBlood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm.\n\nPossible vein assessment or pre-anesthesia evaluation\n\nRecipients will have:\n\nLung test, heart tests, radiology scans, CT scans, and dental exam\n\nPossible tissue biopsies or lumbar puncture\n\nBone marrow and a small piece of bone removed by needle in the hipbone.\n\nChemotherapy 1-2 weeks before transplant day\n\nDonor stem cell donation through a catheter put into a vein in the chest or neck\n\nSeveral-week hospital stay. They will take medications and may need blood transfusions and additional procedures.\n\nAfter discharge, recipients will:\n\nRemain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission.\n\nHave multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years.",[130,131,132,133,134],"Primary T-cell Immunodeficiency Disorders","Common Variable Immunodeficiency","Immune System Diseases","Autoimmune Lymphoproliferative","Lymphoproliferative Disorders",[136,137,138,139,140],"Haploidentical","Autoimmunity","Immune Dysregulation","Congenital","Opportunistic Infection","2026-06-27",{"date":143,"type":144},"2026-06-30","ACTUAL",{"date":146,"type":144},"2015-11-19",{"date":148,"type":124},"2036-12-31",{"name":65,"class":6},2]