Ignite Creation Date:
2025-12-25 @ 2:46 AM
Ignite Modification Date:
2026-03-06 @ 7:41 PM
Study NCT ID:
NCT01998633
Status:
COMPLETED
Last Update Posted:
2022-12-08
First Post:
2013-10-29
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D051359', 'term': 'Lymphohistiocytosis, Hemophagocytic'}, {'id': 'D006105', 'term': 'Granulomatous Disease, Chronic'}, {'id': 'D053306', 'term': 'Hyper-IgM Immunodeficiency Syndrome'}, {'id': 'C535887', 'term': 'Leukocyte adhesion deficiency type 1'}], 'ancestors': [{'id': 'D015616', 'term': 'Histiocytosis, Non-Langerhans-Cell'}, {'id': 'D015614', 'term': 'Histiocytosis'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D010585', 'term': 'Phagocyte Bactericidal Dysfunction'}, {'id': 'D007960', 'term': 'Leukocyte Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D040181', 'term': 'Genetic Diseases, X-Linked'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D004406', 'term': 'Dysgammaglobulinemia'}, {'id': 'D001796', 'term': 'Blood Protein Disorders'}, {'id': 'D000081207', 'term': 'Primary Immunodeficiency Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D033581', 'term': 'Stem Cell Transplantation'}], 'ancestors': [{'id': 'D017690', 'term': 'Cell Transplantation'}, {'id': 'D064987', 'term': 'Cell- and Tissue-Based Therapy'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D014180', 'term': 'Transplantation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'amendizabal@emmes.com', 'phone': '301-251-1161', 'title': 'Adam Mendizabal, PhD', 'organization': 'The Emmes Corporation'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '1 year post-transplant', 'eventGroups': [{'id': 'EG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)', 'otherNumAtRisk': 46, 'otherNumAffected': 0, 'seriousNumAtRisk': 46, 'seriousNumAffected': 14}], 'seriousEvents': [{'term': 'Febrile neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Haemolytic anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Cardiac arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Cardiac disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Ventricular hypertrophy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Death', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Serum sickness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Post transplant lymphoproliferative disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Cerebrovascular accident', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Haemorrhagic stroke', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Posterior reversible encephalopathy syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Proteinuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Respiratory failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'sourceVocabulary': 'MedDRA 20.0'}, {'term': 'Hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 46, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'sourceVocabulary': 'MedDRA 20.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percentage of Participants With Overall Survival (OS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'title': '1 year OS', 'categories': [{'measurements': [{'value': '80.4', 'groupId': 'OG000', 'lowerLimit': '68.6', 'upperLimit': '88.2'}]}]}, {'title': '18 month OS', 'categories': [{'measurements': [{'value': '66.7', 'groupId': 'OG000', 'lowerLimit': '52.9', 'upperLimit': '77.3'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year and 18 months post-transplant', 'description': 'Overall survival is defined as survival of death from any cause.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Overall Survival (OS) by Disease Type', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hemophagocytic Lymphohistiocytosis (HLH)'}, {'id': 'OG001', 'title': 'Other Primary Immune Deficiencies (PID)'}], 'classes': [{'title': '1 year OS', 'categories': [{'measurements': [{'value': '82.4', 'groupId': 'OG000', 'lowerLimit': '68.4', 'upperLimit': '90.6'}, {'value': '75.0', 'groupId': 'OG001', 'lowerLimit': '47.4', 'upperLimit': '89.5'}]}]}, {'title': '18 month OS', 'categories': [{'measurements': [{'value': '68.0', 'groupId': 'OG000', 'lowerLimit': '51.8', 'upperLimit': '79.7'}, {'value': '62.5', 'groupId': 'OG001', 'lowerLimit': '32.7', 'upperLimit': '82.0'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year and 18 months post-transplant', 'description': 'Overall survival is defined as survival of death from any cause.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of HLH Participants With HLH Reactivation Post-Transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'measurements': [{'value': '14.7', 'groupId': 'OG000', 'lowerLimit': '5.2', 'upperLimit': '28.7'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year post-transplant', 'description': 'Systemic HLH Reactivation: Post-transplant HLH reactivation is defined by clinical and lab evidence of pathologic inflammation (persistent fever, progressive cytopenias, rising ferritin and soluble IL2Rα, decreasing fibrinogen, hepatosplenomegaly, end-organ damage) not attributable to other causes.\n\nCentral nervous system (CNS) HLH Reactivation: Reactivation of CNS inflammation in patients with HLH may present with or without altered mental status and is defined by pleocytosis in Cerebrospinal fluid (CSF) or an MRI consistent with CNS inflammation not attributable to other causes.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants with HLH'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Neutrophil Engraftment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'measurements': [{'value': '100.0', 'groupId': 'OG000', 'lowerLimit': '90.8', 'upperLimit': '100.0'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 42 post-transplant', 'description': 'Time to absolute neutrophil count (ANC) engraftment is defined as the first of three measurements on different days that the patient has an absolute neutrophil count of ≥ 500x10\\^6/liter following conditioning regimen induced nadir.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Platelet Engraftment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'measurements': [{'value': '88.9', 'groupId': 'OG000', 'lowerLimit': '73.3', 'upperLimit': '95.6'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 100 post-transplant', 'description': 'Platelet engraftment is defined as the first day of a minimum of three measurements on different days that the patient has achieved a platelet count \\> 20,000 / microliter AND the patient is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants Alive With Sustained Engraftment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'measurements': [{'value': '39.1', 'groupId': 'OG000', 'lowerLimit': '25.1', 'upperLimit': '54.6'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year post-transplant', 'description': 'Sustained engraftment is defined as the occurrence of whole blood donor chimerism \\> 5% by Day 42 accompanied by the absence of any primary or secondary graft failure. Primary graft failure is defined as \\< 5% donor chimerism by Day +42, second stem cell infusion, DLI (except in the case of donor CTLs given for infection control), or second HCT following original HCT. Secondary graft failure is defined as \\< 5% donor chimerism following initial engraftment.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants Alive With Sustained Engraftment by Disease Type', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hemophagocytic Lymphohistiocytosis (HLH)', 'description': 'Participants with Hemophagocytic Lymphohistiocytosis'}, {'id': 'OG001', 'title': 'Other Primary Immune Deficiencies (PID)', 'description': 'Participants with other primary immune deficiencies, including chronic active EBV disease, chronic granulomatous disease, hyper-immunoglobulin M syndrome, and immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome'}], 'classes': [{'categories': [{'measurements': [{'value': '41.2', 'groupId': 'OG000', 'lowerLimit': '24.7', 'upperLimit': '59.3'}, {'value': '33.3', 'groupId': 'OG001', 'lowerLimit': '9.9', 'upperLimit': '65.1'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year post-transplant', 'description': 'Sustained engraftment is defined as the occurrence of whole blood donor chimerism \\> 5% by Day 42 accompanied by the absence of any primary or secondary graft failure. Primary graft failure is defined as \\< 5% donor chimerism by Day +42, second stem cell infusion, DLI (except in the case of donor CTLs given for infection control), or second HCT following original HCT. Secondary graft failure is defined as \\< 5% donor chimerism following initial engraftment.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Acute Graft-Versus-Host Disease (GVHD)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'title': 'Grade 0 or I', 'measurements': [{'value': '35', 'groupId': 'OG000'}]}, {'title': 'Grade II', 'measurements': [{'value': '3', 'groupId': 'OG000'}]}, {'title': 'Grade III', 'measurements': [{'value': '5', 'groupId': 'OG000'}]}, {'title': 'Grade IV', 'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '1 year post-transplant', 'description': 'Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:\n\nSkin stage:\n\n0: No rash\n\n1. Rash \\<25% of body surface area\n2. Rash on 25-50% of body surface area\n3. Rash on \\> 50% of body surface area\n4. Generalized erythroderma with bullous formation\n\nLiver stage (based on bilirubin level)\\*:\n\n0: \\<2 mg/dL\n\n1. 2-3 mg/dL\n2. 3.01-6 mg/dL\n3. 6.01-15.0 mg/dL\n4. \\>15 mg/dL\n\nGI stage\\*:\n\n0: No diarrhea or diarrhea \\<500 mL/day\n\n1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD\n2. Diarrhea 1000-1499 mL/day\n3. Diarrhea \\>1500 mL/day\n4. Severe abdominal pain with or without ileus \\* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.\n\nGVHD grade:\n\n0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'title': 'Grade II-IV Acute GVHD at Day 100', 'categories': [{'measurements': [{'value': '17.4', 'groupId': 'OG000', 'lowerLimit': '8.1', 'upperLimit': '29.7'}]}]}, {'title': 'Grade II-IV Acute GVHD at 6 Months', 'categories': [{'measurements': [{'value': '26.1', 'groupId': 'OG000', 'lowerLimit': '14.4', 'upperLimit': '39.4'}]}]}, {'title': 'Grade III-IV Acute GVHD at Day 100', 'categories': [{'measurements': [{'value': '10.9', 'groupId': 'OG000', 'lowerLimit': '4.0', 'upperLimit': '21.3'}]}]}, {'title': 'Grade III-IV Acute GVHD at 6 Months', 'categories': [{'measurements': [{'value': '17.4', 'groupId': 'OG000', 'lowerLimit': '8.1', 'upperLimit': '29.7'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Day 100 and 6 months post-transplant', 'description': 'Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:\n\nSkin stage:\n\n0: No rash\n\n1. Rash \\<25% of body surface area\n2. Rash on 25-50% of body surface area\n3. Rash on \\> 50% of body surface area\n4. Generalized erythroderma with bullous formation\n\nLiver stage (based on bilirubin level)\\*:\n\n0: \\<2 mg/dL\n\n1. 2-3 mg/dL\n2. 3.01-6 mg/dL\n3. 6.01-15.0 mg/dL\n4. \\>15 mg/dL\n\nGI stage\\*:\n\n0: No diarrhea or diarrhea \\<500 mL/day\n\n1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD\n2. Diarrhea 1000-1499 mL/day\n3. Diarrhea \\>1500 mL/day\n4. Severe abdominal pain with or without ileus \\* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.\n\nGVHD grade:\n\n0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Chronic GVHD', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'title': 'None', 'measurements': [{'value': '34', 'groupId': 'OG000'}]}, {'title': 'Mild', 'measurements': [{'value': '10', 'groupId': 'OG000'}]}, {'title': 'Severe', 'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '1 year post-transplant', 'description': 'Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Chronic GVHD', 'denoms': [{'units': 'Participants', 'counts': [{'value': '46', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'classes': [{'categories': [{'measurements': [{'value': '26.7', 'groupId': 'OG000', 'lowerLimit': '14.6', 'upperLimit': '40.4'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '1 year post-transplant', 'description': 'Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.\n\nHematopoietic Stem Cell Transplant: NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '47'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '46'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Hemophagocytic Lymphohistiocytosis (HLH)', 'description': 'Participants with Hemophagocytic Lymphohistiocytosis'}, {'id': 'BG001', 'title': 'Other Primary Immune Deficiencies (PID)', 'description': 'Participants with other primary immune deficiencies, including chronic active EBV disease, chronic granulomatous disease, hyper-immunoglobulin M syndrome, and immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Customized', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'title': '0-9 Years', 'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '34', 'groupId': 'BG002'}]}, {'title': '10-19 Years', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': '20-29 Years', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '31', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '35', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Karnofsky Performance Score (KPS)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'title': '90-100', 'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '34', 'groupId': 'BG002'}]}, {'title': '80', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': '70', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': '60', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': '50', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'KPS describes patient-perceived global quality of life and functioning on a scale of 0-100.\n\n100: No evidence of disease; 90: Normal activity. Minor signs or symptoms of disease; 80: Normal activity with effort. Some signs or symptoms of disease; 70: Cares for self. Unable to continue normal activity; 60: Needs occasional assistance, but cares for most personal needs; 50: Needs considerable assistance and medical care; 40: Disabled. Needs special care and assistance; 30: Severely disabled. Hospital admission indicated; 20: Very sick. Active supportive therapy needed; 10: Moribund; 0: Dead', 'unitOfMeasure': 'Participants'}, {'title': 'Primary Immune Deficiency Type', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Chronic Active Epstein-Barr Virus', 'measurements': [{'value': '3', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Chronic Granulomatous Disease', 'measurements': [{'value': '5', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'Hyperimmunoglobulin M Syndrome', 'measurements': [{'value': '2', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'IPEX', 'measurements': [{'value': '2', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Participants with Primary Immune Deficiencies'}, {'title': 'Donor Type', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'categories': [{'title': 'HLA Matched Sibling', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}, {'title': '1 HLA Locus Mismatched Relative', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'HLA Matched Unrelated', 'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}, {'title': '1 HLA Locus Mismatched Unrelated', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'HLA matching and relatedness of donor to recipient', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-06-16', 'size': 2754444, 'label': 'Study Protocol, Statistical Analysis Plan, and Informed Consent Form', 'hasIcf': True, 'hasSap': True, 'filename': 'Prot_SAP_ICF_000.pdf', 'typeAbbrev': 'Prot_SAP_ICF', 'uploadDate': '2022-12-01T11:48', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 47}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-12', 'completionDateStruct': {'date': '2016-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-12-06', 'studyFirstSubmitDate': '2013-10-29', 'resultsFirstSubmitDate': '2018-03-29', 'studyFirstSubmitQcDate': '2013-11-25', 'lastUpdatePostDateStruct': {'date': '2022-12-08', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-05-01', 'studyFirstPostDateStruct': {'date': '2013-12-02', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-06-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-09-23', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of Participants With Overall Survival (OS)', 'timeFrame': '1 year and 18 months post-transplant', 'description': 'Overall survival is defined as survival of death from any cause.'}], 'secondaryOutcomes': [{'measure': 'Percentage of Participants With Overall Survival (OS) by Disease Type', 'timeFrame': '1 year and 18 months post-transplant', 'description': 'Overall survival is defined as survival of death from any cause.'}, {'measure': 'Percentage of HLH Participants With HLH Reactivation Post-Transplant', 'timeFrame': '1 year post-transplant', 'description': 'Systemic HLH Reactivation: Post-transplant HLH reactivation is defined by clinical and lab evidence of pathologic inflammation (persistent fever, progressive cytopenias, rising ferritin and soluble IL2Rα, decreasing fibrinogen, hepatosplenomegaly, end-organ damage) not attributable to other causes.\n\nCentral nervous system (CNS) HLH Reactivation: Reactivation of CNS inflammation in patients with HLH may present with or without altered mental status and is defined by pleocytosis in Cerebrospinal fluid (CSF) or an MRI consistent with CNS inflammation not attributable to other causes.'}, {'measure': 'Percentage of Participants With Neutrophil Engraftment', 'timeFrame': 'Day 42 post-transplant', 'description': 'Time to absolute neutrophil count (ANC) engraftment is defined as the first of three measurements on different days that the patient has an absolute neutrophil count of ≥ 500x10\\^6/liter following conditioning regimen induced nadir.'}, {'measure': 'Percentage of Participants With Platelet Engraftment', 'timeFrame': 'Day 100 post-transplant', 'description': 'Platelet engraftment is defined as the first day of a minimum of three measurements on different days that the patient has achieved a platelet count \\> 20,000 / microliter AND the patient is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.'}, {'measure': 'Percentage of Participants Alive With Sustained Engraftment', 'timeFrame': '1 year post-transplant', 'description': 'Sustained engraftment is defined as the occurrence of whole blood donor chimerism \\> 5% by Day 42 accompanied by the absence of any primary or secondary graft failure. Primary graft failure is defined as \\< 5% donor chimerism by Day +42, second stem cell infusion, DLI (except in the case of donor CTLs given for infection control), or second HCT following original HCT. Secondary graft failure is defined as \\< 5% donor chimerism following initial engraftment.'}, {'measure': 'Percentage of Participants Alive With Sustained Engraftment by Disease Type', 'timeFrame': '1 year post-transplant', 'description': 'Sustained engraftment is defined as the occurrence of whole blood donor chimerism \\> 5% by Day 42 accompanied by the absence of any primary or secondary graft failure. Primary graft failure is defined as \\< 5% donor chimerism by Day +42, second stem cell infusion, DLI (except in the case of donor CTLs given for infection control), or second HCT following original HCT. Secondary graft failure is defined as \\< 5% donor chimerism following initial engraftment.'}, {'measure': 'Number of Participants With Acute Graft-Versus-Host Disease (GVHD)', 'timeFrame': '1 year post-transplant', 'description': 'Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:\n\nSkin stage:\n\n0: No rash\n\n1. Rash \\<25% of body surface area\n2. Rash on 25-50% of body surface area\n3. Rash on \\> 50% of body surface area\n4. Generalized erythroderma with bullous formation\n\nLiver stage (based on bilirubin level)\\*:\n\n0: \\<2 mg/dL\n\n1. 2-3 mg/dL\n2. 3.01-6 mg/dL\n3. 6.01-15.0 mg/dL\n4. \\>15 mg/dL\n\nGI stage\\*:\n\n0: No diarrhea or diarrhea \\<500 mL/day\n\n1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD\n2. Diarrhea 1000-1499 mL/day\n3. Diarrhea \\>1500 mL/day\n4. Severe abdominal pain with or without ileus \\* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.\n\nGVHD grade:\n\n0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4'}, {'measure': 'Percentage of Participants With Grade II-IV and Grade III-IV Acute GVHD', 'timeFrame': 'Day 100 and 6 months post-transplant', 'description': 'Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:\n\nSkin stage:\n\n0: No rash\n\n1. Rash \\<25% of body surface area\n2. Rash on 25-50% of body surface area\n3. Rash on \\> 50% of body surface area\n4. Generalized erythroderma with bullous formation\n\nLiver stage (based on bilirubin level)\\*:\n\n0: \\<2 mg/dL\n\n1. 2-3 mg/dL\n2. 3.01-6 mg/dL\n3. 6.01-15.0 mg/dL\n4. \\>15 mg/dL\n\nGI stage\\*:\n\n0: No diarrhea or diarrhea \\<500 mL/day\n\n1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD\n2. Diarrhea 1000-1499 mL/day\n3. Diarrhea \\>1500 mL/day\n4. Severe abdominal pain with or without ileus \\* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.\n\nGVHD grade:\n\n0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4'}, {'measure': 'Number of Participants With Chronic GVHD', 'timeFrame': '1 year post-transplant', 'description': 'Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.'}, {'measure': 'Percentage of Participants With Chronic GVHD', 'timeFrame': '1 year post-transplant', 'description': 'Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Hemophagocytic lymphohistiocytosis', 'Chronic Active EBV', 'Chronic Granulomatous Disease', 'Hyperimmunoglobulin M Syndrome (Hyper IGM)', 'Leukocyte Adhesion Deficiency', 'IPEX', 'Hematopoietic Stem Cell Transplant (HSCT)', 'Non-Myeloablative Transplant (NST)', 'Reduced-Intensity Conditioning (RIC)'], 'conditions': ['Hemophagocytic Lymphohistiocytosis', 'Chronic Active Epstein-Barr Virus Infection', 'Chronic Granulomatous Disease', 'HIGM-1', 'Leukocyte Adhesion Deficiency', 'IPEX']}, 'referencesModule': {'references': [{'pmid': '7581076', 'type': 'BACKGROUND', 'citation': 'Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.'}, {'pmid': '16338616', 'type': 'BACKGROUND', 'citation': 'Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.'}, {'pmid': '37042921', 'type': 'DERIVED', 'citation': 'Geerlinks AV, Scull B, Krupski C, Fleischmann R, Pulsipher MA, Eapen M, Connelly JA, Bollard CM, Pai SY, Duncan CN, Kean LS, Baker KS, Burroughs LM, Andolina JR, Shenoy S, Roehrs P, Hanna R, Talano JA, Schultz KR, Stenger EO, Lin H, Zoref-Lorenz A, McClain KL, Jordan MB, Man TK, Allen CE, Marsh RA. Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT. Blood Adv. 2023 Jul 25;7(14):3725-3734. doi: 10.1182/bloodadvances.2022009478.'}]}, 'descriptionModule': {'briefSummary': "HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent primary immune disorders that are typically fatal without Hematopoietic Cell Transplant (HCT). However, transplant is often complicated by inflammation, infection and other co-morbidities. In addition, these disorders have been shown to be cured with partial chimerism, making them an ideal target for the use of reduced intensity approaches, where a portion of patients may not achieve full donor chimerism, but instead achieve stable mixed chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH (Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and unstable chimerism remain challenges. An institutional case series from Cincinnati Children's Hospital demonstrated full or high-level chimerism and improved durable engraftment using intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH as well as other primary immunodeficiencies where allogeneic transplant with RIC has been shown to be feasible and stable chimerism is curative.", 'detailedDescription': 'The primary goal of this Phase II clinical trial is to determine the one-year overall survival of patients treated for immune deficiencies including HLH, HLH-like disorders, CGD, HIGM1, IPEX syndrome, and severe LAD-I with Matched Related Donor (MRD)/ Matched Unrelated Donor (MUD) bone marrow transplant using a reduced-intensity conditioning strategy including intermediate-timing of alemtuzumab. The donor choice is an unaffected related bone marrow donor who is a 6/6 match at HLA-A, -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) OR a 7/8 or 8/8 match for human leukocyte antigen (HLA)-A, -B, -C and -DRB1 (at high resolution using DNA-based typing), OR an unrelated bone marrow donor who is a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 (at high resolution using DNA-based typing). The transplant conditioning regimen will include fludarabine, melphalan, and alemtuzumab starting at Day -14 (Flu/Mel/Alem). Graft Versus Host Disease (GVHD) prophylaxis will consist of cyclosporine and corticosteroids through engraftment. Post-transplant supportive care will include infection surveillance and prophylaxis, and disease-specific supportive care.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '45 Years', 'minimumAge': '4 Months', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria\n\n1. Patient is ≥ 3 months and ≤ 45 years of age at time of enrollment.\n2. Meets criteria for one of the following immune disorders (2A-2F) requiring HCT:\n\n2A. HLH or related disorder with indication for HCT \\[a. Inherited gene mutation associated with HLH: PRF1, UNC13D (MUNC13-2), STXBP2 (MUNC18-2), STX11, RAB27A (Griscelli syndrome, type 2), SH2D1A (XLP1), XIAP (XLP2), LYST (Chediak-Higashi syndrome) - OR - b. Meets clinical criteria for HLH, refractory to therapy according to HLH-94 or HLH-2004 (dexamethasone/etoposide), or recurrent episodes of hyper-inflammation - OR - c. Meets clinical criteria for HLH, without identified gene defects, with affected sibling - OR - decreased or absent NK cell function at the last evaluation, - OR - a history of CNS inflammation as evidenced by pleocytosis in CSF or MRI evidence of hyper-inflammation in the CNS\\]\n\n2B. CAEBV: Patients with chronic EBV infection (CAEBV) with or without associated lymphoma (in complete remission) or active HLH. Note that this diagnosis is distinct from post-transplant lymphoproliferative disorder/ EBV-associated lymphoproliferative disease (PTLD/LPD). \\[Patients must meet all of the following: a. Severe progressive illness, usually with fever, lymphadenopathy and splenomegaly that either began as primary EBV infection or was associated with markedly elevated antibody titers to EBV viral capsid antibody (≥ 1:5120) or early antigen (≥ 1:640), or markedly elevated EBV DNA in the blood; - AND - b. Infiltration of tissues (e.g., lymph nodes, liver, lungs, CNS, bone marrow, eye, skin) with lymphocytes; - AND - c. Elevated EBV DNA, RNA or proteins in affected tissues; - AND - d. The absence of HIV or post-transplant lymphoproliferative disorder\\]\n\n2C. Chronic granulomatous disease with indication for HCT \\[a. Oxidative burst \\< 10% normal with dihydrorhodamine (DHR) assay - AND - b. Documented CGD mutation(s) in gp91phox, p47phox, p67phox, p22phox or p40phox - AND - c. Severe disease as evidenced by one or more of the following: history of one or more potentially life-threatening infections; inflammatory bowel disease; failure to thrive with height \\<10% for age (unless parent(s) height \\<10%); or autoimmune complication felt to be linked to CGD\\]\n\n2D. X-linked Hyper IgM Syndrome (HIGM1) \\[a. Decreased serum IgG (more than 2 standard deviations below normal for age) - AND - b. Mutation in CD40LG - OR - family history of maternally related males with HIGM1\\]\n\n2E. IPEX Syndrome \\[a. Absent FOXP3+ CD4+ T cells - OR - abnormal function of FOXP3+CD4+ T cells - AND - b. Disease-associated mutation in FoxP3 (bi-allelic in females) - OR - family history of maternally related males with clinical diagnosis of IPEX\\]\n\n2F. Severe Leukocyte Adhesion Deficiency, type I (LAD-I) \\[a. Decreased CD18 expression on neutrophils (\\<5% normal for age) - AND - b. Mutation of ITGB2 - OR - absence of ITGB2 mRNA in leukocytes\\]\n\n3\\. Lansky or Karnofsky performance status ≥ 50%.\n\n4\\. The patient's donor must be willing and able to give bone marrow stem cells and be:\n\na. An unaffected sibling donor who is a 6/6 match at HLA-A and -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) OR b. An unaffected related donor (other than sibling) who is a 7/8 or 8/8 match for HLA-A, -B, -C (at intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) OR c. An unrelated donor who is a 7/8 or 8/8 match at HLA-A, -B, -C, and -DRB1 (at high resolution using DNA-based typing).\n\n5\\. Patient must have adequate organ function as measured by:\n\n1. Cardiac: Left ventricular ejection fraction (LVEF) \\> 40%; or LV shortening fraction (LVSF) \\> 26% by echocardiogram.\n2. Renal: Calculated or radioisotope Glomerular Filtration Rate (GFR) \\> 50 mL/min/1.73m\\^2\n3. Hepatic: Adequate liver function: serum conjugated (direct) bilirubin \\< 2x upper limit of normal for age as per local laboratory (with the exceptions of isolated hyperbilirubinemia due to Gilbert's syndrome, or hyperbilirubinemia as the result of liver inflammation in the setting of persistent, active HLH); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\< 10x upper limit of normal as per local laboratory (with the exception of elevated transaminase levels as the result of liver inflammation in the setting of persistent, active HLH).\n4. Pulmonary: Patient may not be on mechanical ventilation support or have progressive pulmonary infection at the time of transplant; Pulmonary Function Testing (PFT) with forced expiratory volume in one second (FEV1) \\> 50% of normal and Diffusing capacity of the lung for carbon monoxide (DLCO) corrected for Hgb \\> 50% of normal. Patients unable to undergo PFTs should have stable respiratory status with SaO2 \\> 90% on a maximum of 2L/min supplemental oxygen.\n\n 6\\. Signed informed consent.\n\n Exclusion Criteria:\n 1. Hematopoietic stem cell transplant within 6 months of enrollment.\n 2. Uncontrolled bacterial, viral or fungal infection (currently receiving appropriate antimicrobials and experiencing progression or no clinical improvement) at time of enrollment. We recognize that patients with CAEBV may have ongoing EBV viremia at the time of initiating transplant therapy, but other patients should have no uncontrolled bacterial, viral or fungal infections at the time of enrollment (or prior to initiating the preparative regimen).\n 3. Pregnant or breastfeeding.\n 4. Seropositive for human immunodeficiency virus (HIV).\n 5. Alemtuzumab within 2 weeks of enrollment.\n 6. History of prior or current malignancy, especially malignancies with a likelihood of relapse and progression, with the exception of (1) EBV-associated lymphomas related to immune deficiency or lymphomas associated with X-linked LPD in a good remission, as they are unlikely to relapse after treatment; (2) Resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs."}, 'identificationModule': {'nctId': 'NCT01998633', 'acronym': 'RICHI', 'briefTitle': 'Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)', 'organization': {'class': 'OTHER', 'fullName': 'Medical College of Wisconsin'}, 'officialTitle': 'Reduced-Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (RICHI) (BMT CTN #1204)', 'orgStudyIdInfo': {'id': 'BMTCTN1204'}, 'secondaryIdInfos': [{'id': '2U10HL069294-11', 'link': 'https://reporter.nih.gov/quickSearch/2U10HL069294-11', 'type': 'NIH'}, {'id': '5U24CA076518', 'link': 'https://reporter.nih.gov/quickSearch/5U24CA076518', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Hematopoietic Stem Cell Transplant', 'description': 'Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.', 'interventionNames': ['Biological: Hematopoietic Stem Cell Transplant']}], 'interventions': [{'name': 'Hematopoietic Stem Cell Transplant', 'type': 'BIOLOGICAL', 'description': 'NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.\n\n* Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10\n* Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4\n* Melphalan 140mg/m2 on Day -3\n\nThe GVHD prophylaxis will consist of the following:\n\n* Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180.\n* Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)', 'armGroupLabels': ['Hematopoietic Stem Cell Transplant']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama at Birmingham', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': "Children's National Medical Center", 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': "Children's Healthcare of Atlanta", 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '60614-3363', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': "Ann and Robert H. Lurie Children's Hospital of Chicago", 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '21231', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Dana Farber Cancer Institute/Children's Hospital of Boston", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48105-2967', 'city': 'Ann Arbor', 'state': 'Michigan', 'country': 'United States', 'facility': 'University of Michigan Medical Center', 'geoPoint': {'lat': 42.27756, 'lon': -83.74088}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': "Washington University/St. Louis Children's Hospital", 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan-Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '14642', 'city': 'Rochester', 'state': 'New York', 'country': 'United States', 'facility': 'University of Rochester Medical Center', 'geoPoint': {'lat': 43.15478, 'lon': -77.61556}}, {'zip': '27599-7305', 'city': 'Chapel Hill', 'state': 'North Carolina', 'country': 'United States', 'facility': 'University of North Carolina at Chapel Hill', 'geoPoint': {'lat': 35.9132, 'lon': -79.05584}}, {'zip': '27705', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University Medical Center', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}, {'zip': '45229-3039', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': "Cincinnati Children's Hospital Medical Center", 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '97239-3098', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health and Science University', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '75235', 'city': 'Dallas', 'state': 'Texas', 'country': 'United States', 'facility': "Children's Medical Center of Dallas", 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}, {'zip': '76104', 'city': 'Fort Worth', 'state': 'Texas', 'country': 'United States', 'facility': "Cook Children's Medical Center", 'geoPoint': {'lat': 32.72541, 'lon': -97.32085}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Baylor College of Medicine', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '98109-1024', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'Fred Hutchinson Cancer Research Center', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}, {'zip': '53211', 'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'facility': "Midwest Children's Cancer", 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}, {'zip': 'V5Z 4E3', 'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'facility': "British Columbia Children's Hosp-Vancouver", 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'zip': 'H3T1C5', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Hopital Sainte-Justine', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'zip': 'H4A 3J1', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'McGill University - Montreal', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}], 'overallOfficials': [{'name': 'Mary Horowitz, MD, MS', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin'}]}, 'ipdSharingStatementModule': {'url': 'https://biolincc.nhlbi.nih.gov/home/', 'timeFrame': 'Within 6 months of official study closure at participating sites.', 'ipdSharing': 'YES', 'description': 'Findings will be published in a manuscript.', 'accessCriteria': 'Available to the public.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Medical College of Wisconsin', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}, {'name': 'Blood and Marrow Transplant Clinical Trials Network', 'class': 'NETWORK'}, {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}, {'name': 'National Marrow Donor Program', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}