Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim

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Brief Title

Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim

Official Title

Hematopoietic Stem Cell Transplantation for Children With Severe Combined Immunodeficiency Disease Utilizing Alemtuzumab and Mobilization With Plerixafor & Filgrastim

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Engraftment of Donor B-cells in Blood by STR Testing

Secondary Outcome

 Incidence of Acute GVHD

Condition

Severe Combined Immunodeficiency

Intervention

Transplant Conditioning with Mobilization Only

Study Arms / Comparison Groups

 T-cell Graft Permissive SCID
Description:  Patients with SCID with:
i. NK- phenotype; ii. NK+ phenotype with 10/10 HLA-matched relative or unrelated donor; or iii. NK+ phenotype with maternal engraftment by STR analysis and undergoing haplocompatible HSCT from maternal donor Intervention: Transplant Conditioning with Mobilization Only

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

7

Start Date

August 2010

Completion Date

September 2013

Primary Completion Date

September 2013

Eligibility Criteria

        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)
      

Gender

All

Ages

N/A - 3 Years

Accepts Healthy Volunteers

No

Contacts

Christopher C Dvorak, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01182675

Organization ID

UCSF10-00701


Responsible Party

Principal Investigator

Study Sponsor

University of California, San Francisco


Study Sponsor

Christopher C Dvorak, M.D., Principal Investigator, University of California, San Francisco


Verification Date

July 2018