SCID Bu/Flu/ATG Study With T Cell Depletion

NCT ID: NCT02127892

Last Updated: 2017-09-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-02

Study Completion Date

2016-08-01

Brief Summary

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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

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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.

Conditions

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Severe Combined Immunodeficiency

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

unrelated BM with T cell depletion

Intervention Type BIOLOGICAL

Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).

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).

Group Type OTHER

unrelated cord blood

Intervention Type BIOLOGICAL

Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.

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.

Group Type OTHER

haplo BM with T cell depletion

Intervention Type BIOLOGICAL

haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.

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.

Group Type OTHER

unrelated PBSC with T cell depletion

Intervention Type DEVICE

peripheral blood stem cell will be processed for CD34+ cell isolation.

Interventions

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unrelated BM with T cell depletion

Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).

Intervention Type BIOLOGICAL

unrelated cord blood

Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.

Intervention Type BIOLOGICAL

haplo BM with T cell depletion

haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.

Intervention Type BIOLOGICAL

unrelated PBSC with T cell depletion

peripheral blood stem cell will be processed for CD34+ cell isolation.

Intervention Type DEVICE

Other Intervention Names

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CD34+ selection using CliniMACS umbilical cord blood CD34+ selection with CliniMACS CD34+ selection using CliniMACS

Eligibility Criteria

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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.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Neena Kapoor, M.D.

OTHER

Sponsor Role lead

Responsible Party

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Neena Kapoor, M.D.

Professor of Pediatrics, Keck School of Medicine; Division Head, Division of Research Immunology/BMT

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Neena Kapoor, M.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles, University of Southern California

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Countries

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United States

Other Identifiers

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CCI-06-00243

Identifier Type: -

Identifier Source: org_study_id