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SCID Bu/Flu/ATG Study With T Cell Depletion

18. august 2017 oppdatert av: 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.

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

9

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • California
      • Los Angeles, California, Forente stater, 90027
        • Children's Hospital Los Angeles

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

Ikke eldre enn 21 år (Barn, Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Annen: 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 navn:
  • CD34+ selection using CliniMACS
Annen: 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 navn:
  • navlestrengsblod
Annen: 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 navn:
  • CD34+ selection with CliniMACS
Annen: 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.
Enhet: unrelated PBSC with T cell depletion
peripheral blood stem cell will be processed for CD34+ cell isolation.
Andre navn:
  • CD34+ selection using CliniMACS

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Neena Kapoor, M.D.

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

2. januar 2007

Primær fullføring (Faktiske)

1. august 2016

Studiet fullført (Faktiske)

1. august 2016

Datoer for studieregistrering

Først innsendt

19. oktober 2012

Først innsendt som oppfylte QC-kriteriene

29. april 2014

Først lagt ut (Anslag)

1. mai 2014

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

18. september 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

18. august 2017

Sist bekreftet

1. august 2017

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CCI-06-00243

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Ja

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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