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Allogeneic Transplantation For Severe Osteopetrosis

10. juli 2019 opdateret af: Masonic Cancer Center, University of Minnesota

Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis

The purpose of this research is to explore what we believe may be a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

7

Fase

  • Fase 2
  • Fase 3

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater, 55455
        • University of MInnesota, Fairview

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

1 dag til 45 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.

    1. Bones that are uniformly markedly dense based on skeletal survey
    2. No history that would suggest autosomal dominant inheritance
    3. Evidence of hematologic changes that are attributed to the underlying disease, including
  • the need for ongoing transfusions, OR
  • the presence of progressive anemia or thrombocytopenia, OR
  • a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
  • persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.

Exclusion Criteria:

  • Patients >45 years of age
  • Evidence of hepatic failure
  • Pulmonary dysfunction sufficient to significantly increase the risk of transplant.
  • Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
  • Cardiac compromise sufficient to substantially increase the risk of transplantation
  • Severe, stable neurologic impairment.
  • Human immunodeficiency virus (HIV) positivity.
  • Pregnant or lactating females

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: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: marrow graft transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
Medicin: Campath-1H
Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.
Andre navne:
  • Alemtuzumab
Stråling: Total Lymphoid Irradiation
Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).
Andre navne:
  • TLI
Medicin: Busulfan
patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.
Andre navne:
  • Busulfex
Medicin: Fludarabine monophosphate
Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.
Andre navne:
  • Fludara
Procedure: marrow graft transplantation
Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.
Andre navne:
  • HSCT
Aktiv komparator: cord blood transplant conditioning
Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.
Medicin: Campath-1H
Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.
Andre navne:
  • Alemtuzumab
Medicin: Busulfan
patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.
Andre navne:
  • Busulfex
Procedure: umbilical cord blood transplantation
Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.
Andre navne:
  • UCBT
Medicin: Cyclophosphamide
Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.
Andre navne:
  • Cytoxan

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Number of Patients Who Achieved Donor Cell Engraftment
Tidsramme: Day 100
Day 100

Sekundære resultatmål

Resultatmål
Tidsramme
Transplant Related Mortality at 100 Days
Tidsramme: day 100
day 100
Transplant Related Toxicity
Tidsramme: Day 100 post transplant
Day 100 post transplant
Incidence of Grade II - IV Acute Graft-versus-host Disease
Tidsramme: by Day 100 after transplant
by Day 100 after transplant

Samarbejdspartnere og efterforskere

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

Sponsor

Masonic Cancer Center, University of Minnesota

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

1. august 2008

Primær færdiggørelse (Faktiske)

1. juni 2013

Studieafslutning (Faktiske)

1. juni 2013

Datoer for studieregistrering

Først indsendt

16. oktober 2008

Først indsendt, der opfyldte QC-kriterier

16. oktober 2008

Først opslået (Skøn)

20. oktober 2008

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

31. juli 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

10. juli 2019

Sidst verificeret

1. juli 2019

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • MT2008-20
  • 0808M42261 (Anden identifikator: Masonic Cancer Center, University of Minnesota)

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Placeringer

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