Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204) (RICHI)
|Hemophagocytic Lymphohistiocytosis Chronic Active Epstein-Barr Virus Infection Chronic Granulomatous Disease HIGM-1 Leukocyte Adhesion Deficiency IPEX||Biological: Hematopoietic Stem Cell Transplant||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Reduced-Intensity Conditioning for Children and Adults With Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (RICHI) (BMT CTN #1204)|
- Overall survival (OS) [ Time Frame: Year 1 ]OS at one year post-transplant in patients who receive at least one dose of the preparative regimen.
- Sustained Engraftment [ Time Frame: Days 100, 180, 365 ]Sustained engraftment will be considered to have occurred in the absence of primary graft failure: < 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; and secondary graft failure: < 5% donor chimerism following original engraftment.
- HLH Reactivation [ Time Frame: Year 1 ]
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.
Central 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.
To assess the incidence of reactivation, cumulative incidence curves will be computed along with a 95% confidence interval. Death prior to reactivation will be considered as a competing risk.
- Immune Reconstitution [ Time Frame: Days 100 and 365 ]Absolute number of CD3, CD4, CD8, CD16+56 and CD19 cells will be measured by flow cytometry. Immunoglobulin levels (IgG, IgA and IgM) will also be quantified.
- Neutrophil Engraftment [ Time Frame: Day 56 ]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 ≥ 500/uL following conditioning regimen induced nadir.
- Platelet Engraftment [ Time Frame: Day 56 ]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 AND the patient is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.
- Cumulative Incidence of Grade Acute GVHD [ Time Frame: Day 100 ]The cumulative incidence of grade II-IV and grade III-IV acute GVHD will be assessed according to the BMT CTN Manual of Procedures (MOP).
- Cumulative Incidence of Chronic GVHD [ Time Frame: Day 365 ]Incidence and severity of chronic GVHD will be scored according to the BMT CTN MOP.
- Frequency of Transplant-Related Complications [ Time Frame: Day 365 ]
|Actual Study Start Date:||December 2013|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Hematopoietic Stem Cell Transplant
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Biological: Hematopoietic 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.
The GVHD prophylaxis will consist of the following:
Please refer to this study by its ClinicalTrials.gov identifier: NCT01998633
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|Study Director:||Mary Horowitz, MD, MS||Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin|