SCID Bu/Flu/ATG Study With T Cell Depletion

August 18, 2017 updated by: Neena Kapoor, M.D.

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

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).
Other Names:
  • CD34+ selection using CliniMACS
Other: 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).
Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.
Other Names:
  • umbilical cord blood
Other: 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.
haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.
Other Names:
  • CD34+ selection with CliniMACS
Other: 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.
peripheral blood stem cell will be processed for CD34+ cell isolation.
Other Names:
  • CD34+ selection using CliniMACS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
100 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
100 days
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.
1 year
Overall Survival
Time Frame: 1 year
Overalls survival of patient at 1 year post transplant
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2007

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

October 19, 2012

First Submitted That Met QC Criteria

April 29, 2014

First Posted (Estimate)

May 1, 2014

Study Record Updates

Last Update Posted (Actual)

September 18, 2017

Last Update Submitted That Met QC Criteria

August 18, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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