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Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

4. mai 2016 oppdatert av: Fred Hutchinson Cancer Center

Conditioning for Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

PRIMARY OBJECTIVE:

I. Determine the incidence and severity of acute graft-versus-host disease (GvHD).

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy.

II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics.

III. Determine the incidence of donor engraftment.

IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3.

V. Determine the incidence and severity of chronic GvHD.

VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr).

VII. Determine the incidence of relapse.

VIII. Determine relapse-free survival.

IX. Determine the incidence of Epstein-Barr virus (EBV) activation.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed at 1 year.

Studietype

Intervensjonell

Registrering (Faktiske)

23

Fase

  • Fase 2

Kontakter og plasseringer

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

Studiesteder

  • Forente stater
    • Washington
      • Seattle, Washington, Forente stater, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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 60 år (Barn, Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast phase (CP2)
  • Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts)
  • Myelodysplastic syndromes (MDS) ( all risk groups)
  • Other myeloproliferative disorders
  • DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele
  • DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated donors will be collected through the National Marrow Donor Program (NMDP) or other donor centers
  • DONOR: Age 12-75 yrs

Exclusion Criteria:

  • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
  • Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal
  • Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted

  • Impaired renal function (creatinine > 2 times normal or estimated creatinine clearance < 60 ml/min)

    • MALE: ([140 -age in years] x ideal body weight [kg])/72 x serum creatinine (SCr) (mg/dL)
    • FEMALE: .85 x ([140-age in years] x ideal body weight [kg])/72 x SCr (mg/dL)
  • Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or acceleration of HIV replication
  • Female patients who are pregnant or breast feeding
  • Life expectancy severely limited by diseases other than malignancy
  • DONOR: donors who for any reason are unable to tolerate the mobilization and leukapheresis procedure
  • DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive
  • DONOR: female donors who have a positive pregnancy test

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: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Treatment (chemotherapy, PBSC transplant)
Patients receive fludarabine phosphate IV over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic PBSC transplant on day 0. Patients then receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.
Annen: laboratoriebiomarkøranalyse
Korrelative studier
Legemiddel: fludarabin fosfat
Gitt IV
Andre navn:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Legemiddel: metotreksat
Gitt IV
Andre navn:
  • ametopterin
  • Folex
  • metylaminopterin
  • Mexate
  • MTX
Legemiddel: busulfan
Gitt IV
Andre navn:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Biologisk: anti-tymocyttglobulin
Gitt IV
Andre navn:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymfocytt immunglobulin
Fremgangsmåte: stamcelletransplantasjon av perifert blod
Gjennomgå allogen PBSC-transplantasjon
Andre navn:
  • PBPC-transplantasjon
  • PBSC-transplantasjon
  • perifer blodprogenitorcelletransplantasjon
  • transplantasjon, perifer blodstamcelle
Fremgangsmåte: allogen hematopoetisk stamcelletransplantasjon
Gjennomgå allogen PBSC-transplantasjon
Legemiddel: takrolimus
Gis IV og oralt
Andre navn:
  • Prograf
  • FK 506

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Incidence of acute GvHD
Tidsramme: Day 100 post-transplant
Maximum grade of acute GVHD and the number of therapies required to treat GVHD will be determined.
Day 100 post-transplant

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy
Tidsramme: At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3
At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3
Thymoglobulin pharmacokinetics
Tidsramme: On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900
On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900
Incidence of donor cell engraftment
Tidsramme: By day 100
By day 100
Incidence of system toxicities >= grade 3 as graded per CTCAE v.3
Tidsramme: Up to day 100 after transplantation
Up to day 100 after transplantation
Incidence of chronic GvHD
Tidsramme: Day 100
Day 100
Incidence of non-relapse mortality defined as death without history of post-transplant relapse
Tidsramme: At day 100
At day 100
Incidence of non-relapse mortality defined as death without history of post-transplant relapse
Tidsramme: At 1 year
At 1 year
Incidence of relapse
Tidsramme: At 1 year
Defined by either morphological or cytogenetic evidence of chronic myelogenous leukemia (CML), AML, MDS or other myeloproliferative disease in marrow, blood, or other sites, or laboratory evidence of residual disease.
At 1 year
Relapse-free survival
Tidsramme: At 1 year
At 1 year
Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR)
Tidsramme: Up to 1 year
Up to 1 year

Samarbeidspartnere og etterforskere

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

Sponsor

Fred Hutchinson Cancer Center

Samarbeidspartnere

National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)

Etterforskere

  • Hovedetterforsker: H. Joachim Deeg, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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

1. september 2004

Primær fullføring (Faktiske)

1. august 2005

Studiet fullført (Faktiske)

1. april 2016

Datoer for studieregistrering

Først innsendt

22. januar 2010

Først innsendt som oppfylte QC-kriteriene

22. januar 2010

Først lagt ut (Anslag)

26. januar 2010

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

6. mai 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

4. mai 2016

Sist bekreftet

1. mai 2016

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 1913.00 (Annen identifikator: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
  • P30CA015704 (U.S. NIH-stipend/kontrakt)
  • P01HL036444 (U.S. NIH-stipend/kontrakt)
  • NCI-2009-01785 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))

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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