Autoimmune Lymphoproliferative Syndrome, Chediak-Higashi Syndrome, Chronic Granulomatous Disease, Common Variable Immune Deficiency, DiGeorge Syndrome, Hemophagocytic Lymphohistiocytosis, Hyper-IgM, Immune Deficiency Disorders, Immune Dysregulatory Disorders, IPEX, Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome, X-linked Agammaglobulinemia, X-linked Lymphoproliferative Syndrome
Conditions
Keywords
Immune deficiency, Immune disorders, Immune dysregulatory, Reduced Intensity, Alemtuzumab, Campath
Brief summary
This study hypothesizes that a reduced intensity immunosuppressive preparative regimen will establish engraftment of donor hematopoietic cells with acceptable early and delayed toxicity in patients with immune function disorders. A regimen that maximizes host immune suppression is expected to reduce graft rejection and optimize donor cell engraftment.
Interventions
DRUGTransplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan
Between days -23 and -15: alemtuzumab test dose, 3mg IV or SQ Day -14: alemtuzumab, 10mg IV or SQ Day -13: alemtuzumab, 15mg IV or SQ Day -12: alemtuzumab, 20mg IV or SQ Days -8 to -4: fludarabine, 30mg/m2 IV Day -4: thiotepa 4mg/kg IV q 12 hours Day -3: melphalan, 140mg/m2 IV Day 0: stem cell infusion Day +7: G-CSF
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* \</= 28 years of age * Performance status \>/= 40 * DLCO \>/= 40% * LVEF \>/=40% or LVSF \>/=26% * Serum creatinine \< 2x ULN * Liver enzymes \</= 5x ULN * Negative pregnancy test * Suitably matched donor (6/6 matched sib UCB, 8/8 matched sib BM or PBSC, 5-6/6 matched unrelated UCB, 7-8/8 matched unrelated BM, double cord)
Exclusion criteria
* Known diagnosis of HIV I/II * Pregnant or breastfeeding * Uncontrolled invasive fungal or bacterial infections within 1 month prior to starting alemtuzumab * Uncontrolled viral infection within 1 week prior to starting alemtuzumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with donor engraftment | 1 year post transplant |
Secondary
| Measure | Time frame |
|---|---|
| Major Transplant Related Toxicities | 1 years post transplant |
| Time to neutrophil recovery | within 100 days post transplant |
| Number of patient with acute GVHD | 180 days post transplant |
| Number of participants with infectious complications | 2 years post transplant |
| Time to immune reconstitution | 2 years post transplant |
| Overall survival | 2 years post transplant |
| Time to platelet recovery | within 100 days post transplant |
| Number of patients with chronic GVHD | 2 years post transplant |
| Disease free survival | 2 years post transplant |
Countries
United States
Outcome results
None listed