Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Neutrophil Engraftment
Study Overview
Brief Summary
This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.
Detailed Description
Based on diagnosis and clinical history, a determination of the most appropriate regimen will be made based on the following prep plans:
Arm A: Fully Myeloablative Preparative Regimen, Arm B: Reduced Toxicity Ablative Preparative Regimen, Arm C: Reduced Intensity Conditioning, Arm D: No Preparative Regimen
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 50 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of immunodeficiency or histiocytic disorder including the following:
- •Severe combined immunodeficiency (SCID - all variants)
- •Second bone marrow transplant (BMT) for SCID (after graft rejection)
- •Omenn's Syndrome
- •Reticular dysgenesis
- •Wiskott-Aldrich syndrome
- •Major histocompatibility complex (MHC) Class II deficiency (bare lymphocyte syndrome)
- •Hyper IgM Syndrome (CD40 Ligand Deficiency)
- •Common variable immunodeficiency (CVID) with severe phenotype
- •Chronic Granulomatous Disease (CGD)
- •Other severe Combined Immune Deficiencies (CID)
- •Hemophagocytic Lymphohistiocytosis (HLH)
- •X-linked Lymphoproliferative Disease (XLP)
- •Chediak-Higashi Syndrome (CHS)
- •Griscelli Syndrome
- •Langerhans Cell Histiocytosis (LCH)
- •Acceptable stem cell sources include:
- •HLA identical or 1 antigen matched sibling donor eligible to donate bone marrow
- •HLA identical or up to a 1 antigen mismatched unrelated BM donor
- •Sibling donor cord blood with acceptable HLA match and cell dose as per current institutional standards
- •Single unrelated umbilical cord blood unit with 0-2 antigen mismatch and minimum cell dose of >5 x 10^7 nucleated cells/kg as per current institutional guidelines
- •Double unrelated umbilical cord blood units that are:
- •up to 2 antigen mismatched to the patient
- •up to 2 antigen mismatched to each other
- •minimum cell dose of at least one single unit must be ≥ 3.5 x 10^7 nucleated cells/kg
- •combined dose of both units must provide a total cell dose of ≥ 5 x 10^7 nucleated cells/kg
- •Age: 0 to 50 years
- •Adequate organ function and performance status.
Exclusion Criteria
- •pregnant or breastfeeding
- •active, uncontrolled infection and/or HIV positive
- •acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
Arms & Interventions
Arm C: Reduced Intensity Conditioning
For use in patients with diseases including HLH. Receives Alemtuzumab 0.2 mg/kg intravenously (IV) on days -14 through -10, fludarabine phosphate 30 mg/m^2 IV on days -8 through -4, melphalan 140 mg/m^2 IV on day -3 and stem cell infusion on day 0.
Intervention: Alemtuzumab 0.2 mg (Drug)
Arm A: Fully Myeloablative regimen
For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Stem Cell Transplantation (Biological)
Arm B: Reduced Toxicity Ablative Regimen
For use in patients with diseases including SCID, CGD, CHS and other CID. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6, fludarabine phosphate 40 mg/m^2 IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Stem Cell Transplantation (Biological)
Arm B: Reduced Toxicity Ablative Regimen
For use in patients with diseases including SCID, CGD, CHS and other CID. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6, fludarabine phosphate 40 mg/m^2 IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Fludarabine phosphate 40 mg (Drug)
Arm B: Reduced Toxicity Ablative Regimen
For use in patients with diseases including SCID, CGD, CHS and other CID. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6, fludarabine phosphate 40 mg/m^2 IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Busulfan (Drug)
Arm C: Reduced Intensity Conditioning
For use in patients with diseases including HLH. Receives Alemtuzumab 0.2 mg/kg intravenously (IV) on days -14 through -10, fludarabine phosphate 30 mg/m^2 IV on days -8 through -4, melphalan 140 mg/m^2 IV on day -3 and stem cell infusion on day 0.
Intervention: Stem Cell Transplantation (Biological)
Arm D: No Preparative Regimen
For use in patients with complete SCID phenotype with no evidence of maternal engraftment or residual immune function who will be receiving their stem cell transplantation from a genotypically matched donor.
Intervention: Stem Cell Transplantation (Biological)
Arm A: Fully Myeloablative regimen
For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Alemtuzumab 0.3 mg (Drug)
Arm A: Fully Myeloablative regimen
For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Cyclophosphamide (Drug)
Arm A: Fully Myeloablative regimen
For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Busulfan (Drug)
Arm A: Fully Myeloablative regimen
For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: MESNA (Drug)
Arm B: Reduced Toxicity Ablative Regimen
For use in patients with diseases including SCID, CGD, CHS and other CID. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6, fludarabine phosphate 40 mg/m^2 IV on days -5 through -2 and stem cell infusion on day 0.
Intervention: Alemtuzumab 0.3 mg (Drug)
Arm C: Reduced Intensity Conditioning
For use in patients with diseases including HLH. Receives Alemtuzumab 0.2 mg/kg intravenously (IV) on days -14 through -10, fludarabine phosphate 30 mg/m^2 IV on days -8 through -4, melphalan 140 mg/m^2 IV on day -3 and stem cell infusion on day 0.
Intervention: Melphalan (Drug)
Arm C: Reduced Intensity Conditioning
For use in patients with diseases including HLH. Receives Alemtuzumab 0.2 mg/kg intravenously (IV) on days -14 through -10, fludarabine phosphate 30 mg/m^2 IV on days -8 through -4, melphalan 140 mg/m^2 IV on day -3 and stem cell infusion on day 0.
Intervention: Fludarabine phosphate 30 mg (Drug)
Outcomes
Primary Outcomes
Neutrophil Engraftment
Time Frame: Day 42
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.
Secondary Outcomes
- Incidence of Graft Failure(Day 100)
- Disease-Free Survival(6 Months)
- Incidence of Transplant-Related Mortality(6 Months)
- Incidence of Chimerism(Day 100, 6 Months, 1 Year)
- Incidence of Acute Graft-Versus-Host Disease(Day 100)
- Incidence of Chronic Graft-Versus-Host Disease(6 Months and 1 Year)
- Overall Survival(6 Months)