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SCID Bu/Flu/ATG Study With T Cell Depletion

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. Identifier: NCT02127892
Recruitment Status : Terminated (Closed due to slow accrual. Nine subjects enrolled over 7 years.)
First Posted : May 1, 2014
Results First Posted : September 18, 2017
Last Update Posted : September 18, 2017
Information provided by (Responsible Party):
Neena Kapoor, M.D., Children's Hospital Los Angeles

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.

Condition or disease Intervention/treatment Phase
Severe Combined Immunodeficiency Biological: unrelated BM with T cell depletion Biological: unrelated cord blood Biological: haplo BM with T cell depletion Device: unrelated PBSC with T cell depletion Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 2, 2007
Actual Primary Completion Date : August 1, 2016
Actual Study Completion Date : August 1, 2016

Arm Intervention/treatment
unrelated BM with T cell depletion
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.
Biological: unrelated BM with T cell depletion
Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).
Other Name: CD34+ selection using CliniMACS

unrelated cord blood
Acceptable matching for unrelated cord blood will be a genotypic match at 6 of 6 alleles (HLA A, B and DR) or 5 of 6 alleles, but not with mismatches at both alleles of a single locus (e.g. not mismatched for both HLA A alleles).
Biological: unrelated cord blood
Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.
Other Name: umbilical cord blood

haplo BM with T cell depletion
If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors.
Biological: haplo BM with T cell depletion
haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.
Other Name: CD34+ selection with CliniMACS

unrelated PBSC with T cell depletion
The preferred source will be bone marrow, however, if a donor is unable or unwilling to donate bone marrow, peripheral blood stem cells (PBSC) will be allowed.
Device: unrelated PBSC with T cell depletion
peripheral blood stem cell will be processed for CD34+ cell isolation.
Other Name: CD34+ selection using CliniMACS

Primary Outcome Measures :
  1. Number of Participants With Engraftment [ Time Frame: 100 day ]
    Engraftment is defined as recovery of blood counts (neutrophil and platelet engraftment) with cells of donor origin, documented by either bone marrow or peripheral blood chimerism assays after hematopoietic stem cell transplant.

Secondary Outcome Measures :
  1. Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3 [ Time Frame: 1 year ]
    Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects.

Other Outcome Measures:
  1. Number of Participants With Veno-occlusive Disease (VOD) - Moderate and Severe [ Time Frame: 100 days ]
    Evaluation of veno-occlusive disease determined by the presence of the following features; fluid retention, weight gain, leaky capillary syndrome, painful liver enlargement, refractoriness to platelet tranfusion and hyperbilirubinemia

  2. Number of Participants With Graft Versus Host Disease (GVHD) - Grade III or IV [ Time Frame: 1 year ]
    GVHD disease surveillance done by clinical evaluation, to include history, physical examination, specifically for rash, jaundice, liver dysfunction, nausea and vomiting, diarrhea and failure to thrive.

  3. Overall Survival [ Time Frame: 1 year ]
    Overalls survival of patient at 1 year post transplant

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT02127892

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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Neena Kapoor, M.D.
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Principal Investigator: Neena Kapoor, M.D. Children's Hospital Los Angeles, University of Southern California

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Responsible Party: Neena Kapoor, M.D., Professor of Pediatrics, Keck School of Medicine; Division Head, Division of Research Immunology/BMT, Children's Hospital Los Angeles Identifier: NCT02127892    
Other Study ID Numbers: CCI-06-00243
First Posted: May 1, 2014    Key Record Dates
Results First Posted: September 18, 2017
Last Update Posted: September 18, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Neena Kapoor, M.D., Children's Hospital Los Angeles:
Severe Combined Immune Deficiency
HLA-matched unrelated donor
bone marrow
cord blood
peripheral blood
CD34+ selection
T cell depletion
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases