Immune Disorder HSCT Protocol

Study Overview
=================
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.

Official Title
-----------------
A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Immune Function Disorders Using a Reduced Intensity Preparatory Regime

Conditions
-----------------
Immune Deficiency Disorders, Severe Combined Immunodeficiency, Chronic Granulomatous Disease, X-linked Agammaglobulinemia, Wiskott-Aldrich Syndrome, Hyper-IgM, DiGeorge Syndrome, Chediak-Higashi Syndrome, Common Variable Immune Deficiency, Immune Dysregulatory Disorders, Hemophagocytic Lymphohistiocytosis, IPEX, Autoimmune Lymphoproliferative Syndrome, X-linked Lymphoproliferative Syndrome

Intervention / Treatment
-----------------
* Drug: Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preparative<br> | Drug: Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with donor engraftment |  | 1 year post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune deficiency, Immune disorders, Immune dysregulatory, Reduced Intensity, Alemtuzumab, Campath