SCID Bu/Flu/ATG Study With T Cell Depletion

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Brief Title

SCID Bu/Flu/ATG Study With T Cell Depletion

Official Title

Phase I/II Trial of Hematopoietic Stem Cell Transplant (HSCT) for Children With Severe Combined Immune Deficiency (SCID) and Without an HLA-Matched Sibling Donor

Brief Summary

      This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with a
      diagnosis of Severe Combined Immune Deficiency (SCID) who do not have an HLA-matched sibling
      donor. The stem cells will be derived from a 1) matched unrelated donor (MUD), 2) unrelated
      cord blood donor, or 3) a haplo-identical (parental) donor (in descending order of
      preference).Patients will receive a novel conditioning regimen with Busulfan, Fludarabine and
      Anti-thymocyte globulin (ATG) followed by an unrelated donor hematopoietic stem cell
      transplant (HSCT) with T-cell depletion using the CliniMACS device.

Detailed Description

      The study is being conducted to assess the following:

        -  overall survival

        -  event-free survival (events are defined as: death,non-engraftment/2nd transplant, immune
           reconstitution failure)

        -  acute toxicity of the conditioning regimen

        -  engraftment frequency immune reconstitution frequency and tempo acute and chronic
           graft-versus-host disease (GVHD), frequency and severity.

      The outcome from this protocol will be compared to the retrospective cohort consisting of all
      patients who have undergone haplo-identical HSCT for SCID at CHLA from 1984-2006 based on the
      assessment of the above-listed endpoints.

      The CliniMACS device will be used for CD34+ selection in place of the Isolex 300i. The
      CliniMACS CD34 Reagent System is an investigational medical device that has not yet been
      approved by the FDA. This device is used in vitro to select and enrich specific cell
      populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from
      heterogenous hematological cell populations for transplantation in cases where this is
      clinically indicated.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Number of Participants With Engraftment

Secondary Outcome

 Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3


Severe Combined Immunodeficiency


unrelated BM with T cell depletion

Study Arms / Comparison Groups

 unrelated BM with T cell depletion
Description:  Acceptable matching for matched unrelated donor (MUD) bone marrow will be genotypic matches at 10 of 10 HLA alleles (HLA-A, B, C, DR and DQ) or 9 of 10 HLA alleles.


* 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


Estimated Enrollment


Start Date

January 2, 2007

Completion Date

August 1, 2016

Primary Completion Date

August 1, 2016

Eligibility Criteria

        Inclusion Criteria:

          -  All patients with SCID who lack a histocompatible sibling or HLA-matched related donor
             will be considered as candidates for this study protocol.

          -  Eligible patients must have adequate physical function to tolerate the chemotherapy
             conditioning regimen and the HSCT, as measure by:

               1. Renal: creatinine clearance or GFR ≥50 ml/min/1.73m2, and not requiring dialysis

               2. Pulmonary: Because patients with SCID frequently present with infectious
                  pneumonia causing ventilatory failure, patients will be considered for enrollment
                  in the study even if respiratory failure requiring mechanical ventilatory support
                  is present. In patients recently diagnosed with pneumonia, efforts to stabilize
                  the respiratory status will be made prior to enrollment in the study.

               3. Infectious disease status. The presence of infection per se will not be a reason
                  for exclusion from the study. Patients with SCID are frequently infected with
                  both routine pathogens as well as opportunistic infections. Antibiotic,
                  antifungal and antiviral prophylaxis and therapy will be instituted as clinically
                  indicated. Despite the use of antimicrobial therapy, the ability to control
                  infections will not be achieved unless HSCT is performed. Therefore, subjects may
                  be enrolled in the study, even though infection is present, because control of
                  infection may depend on engraftment of a donor immune system.

               4. Patients will be 0-21 years of age.

        Exclusion Criteria:

          -  Patient with histocompatible sibling or other related donor

          -  End-organ failure that precludes the ability to tolerate the transplant procedure,
             including conditioning.

          -  Renal failure requiring dialysis

          -  Congenital heart disease resulting in congestive heart failure

          -  Severe CNS disease, e.g., coma or intractable seizures

          -  Ventilatory failure due to non-infectious etiology

          -  Major congenital anomalies that adversely affect survival, eg CNS malformations

          -  Metabolic diseases that would affect transplant survival, eg urea cycle disorders

          -  HIV infection

        Since the only chance of survival for patients with SCID is successful transplantation, all
        patients with SCID will be considered to be potential subjects for the study, regardless of
        end-organ dysfunction.




N/A - 21 Years

Accepts Healthy Volunteers



Neena Kapoor, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Neena Kapoor, M.D.

Study Sponsor

Neena Kapoor, M.D., Principal Investigator, Children's Hospital Los Angeles, University of Southern California

Verification Date

August 2017