Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
- Conditions
- Omenn's SyndromeWiskott-Aldrich SyndromeBare Lymphocyte SyndromeSCIDHemophagocytic LymphohistiocytosisLangerhan's Cell HistiocytosisReticular DysgenesisCommon Variable ImmunodeficiencyHyper IgM SyndromeGriscelli Syndrome
- Interventions
- Registration Number
- NCT01652092
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
-
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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm A: Fully Myeloablative regimen Alemtuzumab 0.3 mg 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. Arm B: Reduced Toxicity Ablative Regimen Alemtuzumab 0.3 mg 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. Arm C: Reduced Intensity Conditioning Alemtuzumab 0.2 mg 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. Arm C: Reduced Intensity Conditioning Fludarabine phosphate 30 mg 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. Arm A: Fully Myeloablative regimen Stem Cell Transplantation 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. Arm B: Reduced Toxicity Ablative Regimen Stem Cell Transplantation 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. Arm C: Reduced Intensity Conditioning Stem Cell Transplantation 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. Arm B: Reduced Toxicity Ablative Regimen Fludarabine phosphate 40 mg 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. Arm D: No Preparative Regimen Stem Cell Transplantation 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. Arm A: Fully Myeloablative regimen Cyclophosphamide 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. Arm A: Fully Myeloablative regimen Busulfan 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. Arm A: Fully Myeloablative regimen MESNA 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. Arm B: Reduced Toxicity Ablative Regimen Busulfan 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. Arm C: Reduced Intensity Conditioning Melphalan 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.
- Primary Outcome Measures
Name Time Method Neutrophil Engraftment 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 Outcome Measures
Name Time Method Incidence of Graft Failure Day 100 Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
Disease-Free Survival 6 Months the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
Incidence of Transplant-Related Mortality 6 Months In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Incidence of Chimerism Day 100, 6 Months, 1 Year a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease.
Incidence of Acute Graft-Versus-Host Disease Day 100 Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Incidence of Chronic Graft-Versus-Host Disease 6 Months and 1 Year Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Overall Survival 6 Months Overall survival will be defined as time from enrollment to date of death or censored at the date of last documented contact for patients still alive.
Trial Locations
- Locations (1)
Masonic Cancer Center, University of Minnesota
🇺🇸Minneapolis, Minnesota, United States