Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
| Status: | Terminated |
|---|---|
| Conditions: | Infectious Disease, HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | Any - 3 |
| Updated: | 8/2/2018 |
| Start Date: | August 2010 |
| End Date: | September 2013 |
Hematopoietic Stem Cell Transplantation for Children With Severe Combined Immunodeficiency Disease Utilizing Alemtuzumab and Mobilization With Plerixafor & Filgrastim
The goal of this study is to develop a novel approach to hematopoietic stem cell
transplantation for children with Severe Combined Immunodeficiency Disease (SCID) that
eliminates the use of toxic chemotherapy conditioning and maximizes the likelihood of T and B
cell immune reconstitution. Rather than classic chemotherapeutic agents, the investigators
will utilize a targeted stem cell mobilizer, plerixafor, in combination with alemtuzumab, a
monoclonal antibody. Correlative scientific questions will include: 1) efficacy and
characteristics of host stem cell mobilization; and 2) alemtuzumab pharmacokinetics in very
young children.
transplantation for children with Severe Combined Immunodeficiency Disease (SCID) that
eliminates the use of toxic chemotherapy conditioning and maximizes the likelihood of T and B
cell immune reconstitution. Rather than classic chemotherapeutic agents, the investigators
will utilize a targeted stem cell mobilizer, plerixafor, in combination with alemtuzumab, a
monoclonal antibody. Correlative scientific questions will include: 1) efficacy and
characteristics of host stem cell mobilization; and 2) alemtuzumab pharmacokinetics in very
young children.
The goal of this study is to develop an approach to hematopoietic stem cell transplantation
for children with Severe Combined Immunodeficiency Disease (SCID) that eliminates the use of
toxic chemotherapy conditioning and maximizes the likelihood of T and B cell immune
reconstitution. SCID is a rare primary immunodeficiency disease in which there are multiple
genotypes and phenotypes, and depending on various factors including the presence of B cell
and NK cells, and the presence of maternal cells in the patient's circulation, there are
numerous ways to approach a transplant. The major issues that must be addressed in any
approach to transplantation for SCID are graft rejection and T and B cell immune
reconstitution. Depending on the specific SCID diagnosis, the phenotype, and the presence of
maternal engraftment at diagnosis, we will evaluate two transplant approaches that will
attempt to optimize the engraftment of donor HSC and the likelihood of T and B cell
reconstitution while eliminating the use of toxic chemotherapy conditioning.
1. Primary Objective: To determine if the administration of plerixafor & filgrastim (G-CSF)
prior to stem cell infusion results in increased donor stem cell occupancy of available
bone marrow niches and B-cell engraftment in patients with SCID.
2. Secondary Objectives:
i. To determine if NK cell depletion with Alemtuzumab will overcome NK-mediated graft
resistance in haplocompatible transplants for NK+ SCID.
ii. To determine the optimal dosing of Alemtuzumab in very young children. iii. To determine
the immunophenotypic characteristics of CD34+ cells mobilized and engrafted in patients
receiving plerixafor & filgrastim prior to HCT.
iv. To determine the thymic output, as measured by T-cell receptor excision circles, in
patients receiving haplocompatible transplants & boosts.
for children with Severe Combined Immunodeficiency Disease (SCID) that eliminates the use of
toxic chemotherapy conditioning and maximizes the likelihood of T and B cell immune
reconstitution. SCID is a rare primary immunodeficiency disease in which there are multiple
genotypes and phenotypes, and depending on various factors including the presence of B cell
and NK cells, and the presence of maternal cells in the patient's circulation, there are
numerous ways to approach a transplant. The major issues that must be addressed in any
approach to transplantation for SCID are graft rejection and T and B cell immune
reconstitution. Depending on the specific SCID diagnosis, the phenotype, and the presence of
maternal engraftment at diagnosis, we will evaluate two transplant approaches that will
attempt to optimize the engraftment of donor HSC and the likelihood of T and B cell
reconstitution while eliminating the use of toxic chemotherapy conditioning.
1. Primary Objective: To determine if the administration of plerixafor & filgrastim (G-CSF)
prior to stem cell infusion results in increased donor stem cell occupancy of available
bone marrow niches and B-cell engraftment in patients with SCID.
2. Secondary Objectives:
i. To determine if NK cell depletion with Alemtuzumab will overcome NK-mediated graft
resistance in haplocompatible transplants for NK+ SCID.
ii. To determine the optimal dosing of Alemtuzumab in very young children. iii. To determine
the immunophenotypic characteristics of CD34+ cells mobilized and engrafted in patients
receiving plerixafor & filgrastim prior to HCT.
iv. To determine the thymic output, as measured by T-cell receptor excision circles, in
patients receiving haplocompatible transplants & boosts.
Inclusion Criteria:
- Patients with classic SCID phenotype (<400 CD3/ul or maternally engrafted and <10% of
normal PHA lymphoproliferative response). Genotypic identification is preferable, but
not required.
- Patients must have an acceptable stem cell donor (HLA matched relative, 9 or 10/10
HLA-matched unrelated, or haplocompatible relative).
Exclusion Criteria:
- Patients with "leaky" SCID syndromes, Omenn's Syndrome, reticular dysgenesis, ADA
deficiency
- Lansky score <60%
- Patient with expected survival <4 weeks (including disseminated CMV infection
involving lungs and/or CNS)
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