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SCID Bu/Flu/ATG Study With T Cell Depletion

18. august 2017 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

9

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90027
        • Children's Hospital Los Angeles

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

Ikke ældre end 21 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Andet: 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.
Biologisk: unrelated BM with T cell depletion
Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).
Andre navne:
  • CD34+ selection using CliniMACS
Andet: 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).
Biologisk: unrelated cord blood
Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.
Andre navne:
  • navlestrengsblod
Andet: 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.
Biologisk: haplo BM with T cell depletion
haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.
Andre navne:
  • CD34+ selection with CliniMACS
Andet: 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.
Enhed: unrelated PBSC with T cell depletion
peripheral blood stem cell will be processed for CD34+ cell isolation.
Andre navne:
  • CD34+ selection using CliniMACS

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Engraftment
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3
Tidsramme: 1 year
Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects.
1 year

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Veno-occlusive Disease (VOD) - Moderate and Severe
Tidsramme: 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
Tidsramme: 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
Tidsramme: 1 year
Overalls survival of patient at 1 year post transplant
1 year

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Neena Kapoor, M.D.

Efterforskere

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

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. januar 2007

Primær færdiggørelse (Faktiske)

1. august 2016

Studieafslutning (Faktiske)

1. august 2016

Datoer for studieregistrering

Først indsendt

19. oktober 2012

Først indsendt, der opfyldte QC-kriterier

29. april 2014

Først opslået (Skøn)

1. maj 2014

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. september 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

18. august 2017

Sidst verificeret

1. august 2017

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CCI-06-00243

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ja

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