Immune Disorder HSCT Protocol

Sponsor

Washington University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT01821781

Collaborator

(none)

Enrollment

Location

Arm

132

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2013

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Preparative	Drug: Transplant 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

Arm

Intervention/Treatment

Experimental: Preparative

Drug: Transplant 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

Outcome Measures

Primary Outcome Measures

Number of participants with donor engraftment [1 year post transplant]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

</= 21 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