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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. maj 2016 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret 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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

23

Fase

  • Fase 2

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Washington
      • Seattle, Washington, Forenede Stater, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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 60 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

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

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: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Andet: laboratoriebiomarkøranalyse
Korrelative undersøgelser
Medicin: fludarabin fosfat
Givet IV
Andre navne:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Medicin: methotrexat
Givet IV
Andre navne:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Medicin: busulfan
Givet IV
Andre navne:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Biologisk: anti-thymocyt globulin
Givet IV
Andre navne:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymfocyt immunglobulin
Procedure: perifer blodstamcelletransplantation
Gennemgå allogen PBSC-transplantation
Andre navne:
  • PBPC transplantation
  • PBSC transplantation
  • transplantation af perifer blodprogenitorcelle
  • transplantation, perifer blodstamcelle
Procedure: allogen hæmatopoietisk stamcelletransplantation
Gennemgå allogen PBSC-transplantation
Medicin: tacrolimus
Gives IV og oralt
Andre navne:
  • Prograf
  • FK 506

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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

Samarbejdspartnere og efterforskere

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

Sponsor

Fred Hutchinson Cancer Center

Samarbejdspartnere

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

Efterforskere

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

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. september 2004

Primær færdiggørelse (Faktiske)

1. august 2005

Studieafslutning (Faktiske)

1. april 2016

Datoer for studieregistrering

Først indsendt

22. januar 2010

Først indsendt, der opfyldte QC-kriterier

22. januar 2010

Først opslået (Skøn)

26. januar 2010

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

6. maj 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

4. maj 2016

Sidst verificeret

1. maj 2016

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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