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

This study has been terminated.
(Insufficient evidence of efficacy)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01182675
First Posted: August 17, 2010
Last Update Posted: December 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Christopher Dvorak, University of California, San Francisco
  Purpose
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.

Condition Intervention Phase
Severe Combined Immunodeficiency Drug: Transplant Conditioning with Mobilization Only Drug: Transplant Conditioning with Mobilization and Alemtuzumab Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplantation for Children With Severe Combined Immunodeficiency Disease Utilizing Alemtuzumab and Mobilization With Plerixafor & Filgrastim

Resource links provided by NLM:


Further study details as provided by Christopher Dvorak, University of California, San Francisco:

Primary Outcome Measures:
  • Engraftment of Donor B-cells in Blood by STR Testing [ Time Frame: 1 Year ]
    Number of participants in whom donor B cells were detected in the patient's blood after HSCT.


Secondary Outcome Measures:
  • Incidence of Acute GVHD [ Time Frame: 100 Days ]
  • Incidence of Chronic GVHD [ Time Frame: 2 Years ]
  • Percentage of Patients Who Become Independent From Regular IVIG Infusion [ Time Frame: 2 Years ]
    Based on B-cell function assays from the patient's blood, we will be able to determine if patients are able to successfully discontinue IVIG infusions.

  • Percent Engraftment of Donor Stem Cells in Bone Marrow by STR Testing [ Time Frame: 1 Year ]
    We will measure whether we are able to detect donor stem cells in the patient's bone marrow after HSCT.

  • Percent Engraftment of Donor T-cells in Blood by STR Testing [ Time Frame: 1 Year ]
    We will measure whether we are able to detect donor T-cells in the patient's blood after HSCT.


Enrollment: 7
Study Start Date: August 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T-cell Graft Permissive SCID

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

Drug: Transplant Conditioning with Mobilization Only
Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0 Transplant
Other Name: Conditioning with Filgrastim and Plerixafor
Experimental: T-cell Graft Resistant SCID
Patients with SCID with NK+ phenotype with HLA-mismatched donor Intervention: Transplant Conditioning with Mobilization and Alemtuzumab
Drug: Transplant Conditioning with Mobilization and Alemtuzumab
Day -7: Alemtuzumab 0.3 mg test dose then 0.3 mg/kg IV; Day -6: Alemtuzumab 0.3 mg/kg IV; Day -5: Alemtuzumab 0.3 mg/kg IV; Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0: Transplant
Other Name: Conditioning with Filgrastim, Plerixafor, and Alemtuzumab

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 3 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01182675


Locations
United States, California
UCSF Benioff Children's Hospital
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Christopher C Dvorak, M.D. University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: Christopher Dvorak, Assistant Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01182675     History of Changes
Other Study ID Numbers: UCSF10-00701
First Submitted: August 9, 2010
First Posted: August 17, 2010
Results First Submitted: October 28, 2014
Results First Posted: November 10, 2014
Last Update Posted: December 1, 2017
Last Verified: October 2017

Keywords provided by Christopher Dvorak, University of California, San Francisco:
SCID
Transplant
Alemtuzumab
Plerixafor

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Lenograstim
Alemtuzumab
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents