Bare Lymphocyte Syndrome, CD40 Ligand Deficiency, Chediak-Higashi Syndrome, Chronic Granulomatous Disease, Common Variable Immunodeficiency, Griscelli Syndrome, Hemophagocytic Lymphohistiocytosis, Hyper IgM Syndrome, Langerhan's Cell Histiocytosis, Omenn's Syndrome, Reticular Dysgenesis, SCID, Wiskott-Aldrich Syndrome, X-linked Lymphoproliferative Disease
Conditions
Keywords
immunodeficiency disorder, histiocytic disorder
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
Interventions
DRUGAlemtuzumab 0.3 mg
0.3 mg/kg intravenously (IV) on days -12 through -10
DRUGCyclophosphamide
cyclophosphamide 50 mg/kg IV on days -9 through -6
DRUGBusulfan
busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2
BIOLOGICALStem Cell Transplantation
Unrelated donor bone marrow will be collected in the usual manner using established parameters determined by the National Marrow Donor Program. A minimum of 3 x 10\^8 nucleated cells/kg recipient weight will be collected with a goal of ≥ 5 x 10\^8 nucleated cells/kg recipient weight. Umbilical cord blood selection will be per the current University of Minnesota Cord Blood Unit Selection algorithm. One or two units may be used to obtain the minimum cell dose. One of the UCB units selected for transplantation must contain ≥ 3.5 x 10\^7 nucleated cells/kg recipient weight based on cell numbers at time of cryopreservation, and the total combined cell dose of both units must be \> 5.0 x 10\^7 nucleated cells/kg.
DRUGFludarabine phosphate 40 mg
40 mg/m\^2 IV on days -5 through -2 (for children \< 6 months and/or \< 10 kg weight dose at 1.33 mg/kg)
DRUGMelphalan
140 mg/m\^2 IV on day -3
DRUGAlemtuzumab 0.2 mg
0.2 mg/kg intravenously (IV) on days -14 through -10
DRUGFludarabine phosphate 30 mg
fludarabine 30 mg/m\^2 IV on days -8 through -4
DRUGMESNA
administered as per the standard institutional protocol.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 50 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMeera Srikanthan, MD
Masonic Cancer Center, University of Minnesota
Outcome results
None listed