A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
National Cancer Institute (NCI)
Summary
Background: During a transplant, blood stem cells from one person are given to someone else. The cells grow into the different cells that make up the immune system. This can cure people with certain immunodeficiencies. But transplant has many risks and complications. Objective: To see if stem cell transplant can be successfully performed in people with primary immunodeficiency disease and cure them. Eligibility: People ages 4-69 for whom a primary immunodeficiency (PID) or Primary Immune Regulatory Disorder (PIRD), has caused significant health problems and either standard management has not worked or there are no standard management options, along with their donors Design: Donors will be screened under protocol 01-C-0129. They will donate blood or bone marrow. Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests CT or PET scans Before transplant, participants will have dental and eye exams. They will have a bone marrow biopsy. For this, a needle will be inserted through the skin into the pelvis to remove marrow. Participants will be hospitalized before their transplant. They will have a central catheter put into a vein in their chest or neck. They will get medications through the catheter to prevent complications. Participants will get stem cells through the catheter. They will stay in the hospital for at least 4 weeks. They will give blood, urine, bone marrow, and stool samples. They may need blood transfusions. They may need more scans. They will take more medications. Participants will have visits on days 30, 60, 100, 180, and 360, and 24 months after the transplant. Then they will have visits once a year for about 5 years
Description
Background: * With the availability of whole exome sequencing (WES) and whole genome sequencing (WGS) for patients with suspected inborn errors of immunity (IEI), the number of recognized IEI has increased in recent years to over 400 distinct immune defects. * Allogeneic hematopoietic stem cell transplantation (HSCT) represents a potentially curative therapy for many hematologic diseases. * Hematopoietic stem cell transplant is now an accepted standard or an appropriate experimental approach for treatment of an increasing number of IEI * We propose to evaluate the efficacy and safety of allog…
Eligibility
- Age range
- 4–69 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIAl: * Age \>= 4 years and \<=69 yo with Weight \>=12 kilograms * Mutation in a known monogenic (IEI) gene performed by a CLIA certified laboratory, who have failed standard medical management, or when no standard medical management is available. OR Patients without a known IEI mutation may be eligible if they have a clinical history that is characteristic of an individual with an immune defect including a history of infections requiring prolonged courses of therapy or evidence of immune dysregulation manifested by autoimmune/autoinflammatory disease, atopy, hemophagocytic…
Interventions
- DrugBusulfan test dose
0.8 mg/kg IV infusion over 2 hours
- DrugFludarabine
40 mg/m2 IV infusion over 30 min once daily for 4 days
- DrugBusulfan
AUC Targeted Dose based on busulfan test dose PKs, IV infusion over 3 hours once daily (3.2 mg/kg IV per day will be the default dose) per the below time frame: For 10/10 Matched Related and Unrelated Donor Recipients For the High Intensity Arm, the busulfan dose will be given for 4 days (-6, -5, -4, and -3). For Intermediate Intensity Arm, the busulfan dose will be given for 3 days (-6,-5, and -4). For Low Intensity Arm, the busulfan dose will be given for 2 days on days (-6 and -5). 9/10 HLA Matched Related or Unrelated Donor Recipients For the High Intensity Arm, the busulfan dose will be given for 3 days (-6, -5, and -4). For the the Intermediate Intensity Arm, the busulfan dose will be given for 2 days (-6 and -5). For the Low Intensity Arm, the busulfan dose will be given for 1 day on day (-6).
- DrugAlemtuzumab
Alemtuzumab will be given if there is evidence of immune dysregulation 10 mg/m2 SC divided over three days (-14, -13, and -12)
- RadiationTotal body Irradiation
Location
- National Institutes of Health Clinical CenterBethesda, Maryland