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Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

29. januar 2019 oppdatert av: National Cancer Institute (NCI)

Phase II Study of Maintenance Therapy With Decitabine (NSC #127716) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years

This phase II trial is studying the side effects and how well decitabine works when given as maintenance therapy after standard therapy in treating patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin, etoposide, busulfan, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine as maintenance therapy after standard therapy may keep cancer cells from coming back.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

PRIMARY OBJECTIVES:

I. To determine the efficacy, feasibility, and toxicities when one year of maintenance therapy with decitabine is given to patients < 60 years with untreated acute myeloid leukemia (AML) who achieve and maintain first complete remission (CR) following an established induction and intensification regimen.

II. To determine the 1-year disease free survival rate for AML patients in first CR treated with maintenance decitabine.

SECONDARY OBJECTIVES:

I. To measure biologic response to decitabine in evaluable patients with fusion genes to determine eradication of minimal residual disease.

II. To measure surrogates for deoxyribonucleic acid (DNA) demethylation including downregulation of DNA methyltransferase 1 (DNMT1) and induction of fetal hemoglobin.

III. To examine the significance of gene re expression following ex vivo decitabine exposure in primary AML cells taken at the time of diagnosis on clinical outcome and on gene expression at the time of relapse after in vivo decitabine exposure.

IV. To continue to evaluate the effectiveness of a cytogenetically risk-adapted approach for consolidation therapy for patients with core binding factor (CBF) or non-CBF AML.

V. To continue the investigation begun in Cancer and Leukemia Group B (CALGB) 19808 aimed at correlation of the rate of relapse and toxicity with intravenous (IV) busulfan pharmacokinetics when busulfan and etoposide are used as the preparative regimen for autologous stem cell transplantation for AML patients in first CR.

VI. To correlate outcome measures such as complete response (CR), disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), with pretreatment characteristics such as age, sex, race, blood counts, morphology, immunophenotype, cytogenetics, and molecular features of AML.

OUTLINE:

REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 168 hours on days 1-7 and daunorubicin hydrochloride IV over 5-10 minutes and etoposide IV over 2 hours on days 1-3. Patients undergo bone marrow biopsy on day 14. Patients with residual leukemia proceed to second remission induction therapy. Patients achieving complete remission (CR) proceed to intensification therapy.

SECOND REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 120 hours on days 1-5 and daunorubicin hydrochloride IV and etoposide IV over 2 hours on days 1 and 2. Patients undergo bone marrow biopsy on day 42. Patients with residual leukemia are removed from the study. Patients achieving CR proceed to intensification therapy.

INTENSIFICATION THERAPY: Patients are stratified and receive intensification therapy according to cytogenetic findings (favorable cytogenetics [t(8;21)(q22q22), inv(16)(p13;q22), or t(16;16)(p13;q22) by cytogenetic and/or molecular analysis] vs unfavorable cytogenetics [all other cytogenetic findings, including normal cytogenetics]).

FAVORABLE CYTOGENETICS: Within 2-4 weeks after achieving CR, patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5.

Treatment repeats every 28 days for up to 3 courses.

UNFAVORABLE CYTOGENETICS: Peripheral blood stem cell (PBSC) mobilization: Within 2-4 weeks after achieving CR, patients receive etoposide IV over 96 hours and high-dose cytarabine IV over 2 hours twice daily on days 1-4 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 14 and continuing until blood counts recover. Patients then proceed to transplantation.

PBSC OR BONE MARROW TRANSPLANTATION: Patients receive busulfan IV over 2 hours 4 times daily on days -7 to -4 and etoposide IV over 4 hours on day -3. Patients undergo autologous PBSC or bone marrow transplantation on day 0 and receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.

UNFAVORABLE CYTOGENETICS AND UNABLE TO UNDERGO PBSC TRANSPLANTATION: Within 2-4 weeks after achieving CR, patients receive etoposide, high-dose cytarabine, and G-CSF as in unfavorable cytogenetics (PBSC mobilization) followed by 2 courses of high-dose cytarabine as in favorable genetics.

MAINTENANCE THERAPY: Within 60-90 days after completion of intensification therapy, patients receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 6 weeks for up to 8 courses.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 2 years, and then yearly for 2 years.

Studietype

Intervensjonell

Registrering (Faktiske)

546

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
    • California
      • San Francisco, California, Forente stater, 94115
        • UCSF Medical Center-Mount Zion
    • Delaware
      • Lewes, Delaware, Forente stater, 19958
        • Beebe Medical Center
      • Newark, Delaware, Forente stater, 19718
        • Christiana Care Health System-Christiana Hospital
    • Florida
      • Orlando, Florida, Forente stater, 32803
        • Florida Hospital Orlando
    • Georgia
      • Atlanta, Georgia, Forente stater, 30342
        • Blood and Marrow Transplant Group of Georgia
    • Illinois
      • Chicago, Illinois, Forente stater, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, Forente stater, 60612
        • University of Illinois
      • Evanston, Illinois, Forente stater, 60201
        • NorthShore University HealthSystem-Evanston Hospital
    • Indiana
      • Fort Wayne, Indiana, Forente stater, 46845
        • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Iowa
      • Iowa City, Iowa, Forente stater, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Maine
      • Bangor, Maine, Forente stater, 04401
        • Eastern Maine Medical Center
    • Maryland
      • Baltimore, Maryland, Forente stater, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bethesda, Maryland, Forente stater, 20889-5600
        • Walter Reed National Military Medical Center
      • Elkton, Maryland, Forente stater, 21921
        • Union Hospital of Cecil County
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, Forente stater, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, Forente stater, 02114
        • Massachusetts General Hospital Cancer Center
      • Worcester, Massachusetts, Forente stater, 01605
        • Commonwealth Hematology Oncology PC-Worcester
    • Missouri
      • Columbia, Missouri, Forente stater, 65212
        • University of Missouri - Ellis Fischel
      • Columbia, Missouri, Forente stater, 65201
        • Veterans Administration
      • Saint Louis, Missouri, Forente stater, 63110
        • Washington University School of Medicine
    • Nebraska
      • North Platte, Nebraska, Forente stater, 69101
        • Great Plains Health Callahan Cancer Center
      • Omaha, Nebraska, Forente stater, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, Forente stater, 89109
        • Sunrise Hospital and Medical Center
      • Las Vegas, Nevada, Forente stater, 89102
        • University Medical Center of Southern Nevada
      • Las Vegas, Nevada, Forente stater, 89106
        • Nevada Cancer Research Foundation CCOP
    • New Hampshire
      • Keene, New Hampshire, Forente stater, 03431
        • Cheshire Medical Center-Dartmouth-Hitchcock Keene
      • Lebanon, New Hampshire, Forente stater, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Camden, New Jersey, Forente stater, 08103
        • Cooper Hospital University Medical Center
    • New York
      • Buffalo, New York, Forente stater, 14263
        • Roswell Park Cancer Institute
      • Lake Success, New York, Forente stater, 11042
        • Northwell Health NCORP
      • Lake Success, New York, Forente stater, 11042
        • Northwell Health/Center for Advanced Medicine
      • Manhasset, New York, Forente stater, 11030
        • North Shore University Hospital
      • New Hyde Park, New York, Forente stater, 11040
        • Long Island Jewish Medical Center
      • New York, New York, Forente stater, 10029
        • Mount Sinai Hospital
      • Syracuse, New York, Forente stater, 13210
        • State University of New York Upstate Medical University
    • North Carolina
      • Chapel Hill, North Carolina, Forente stater, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Goldsboro, North Carolina, Forente stater, 27534
        • Wayne Memorial Hospital
      • Winston-Salem, North Carolina, Forente stater, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Columbus, Ohio, Forente stater, 43210
        • Ohio State University Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, Forente stater, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forente stater, 15224
        • West Penn Hospital
    • Rhode Island
      • Providence, Rhode Island, Forente stater, 02903
        • Rhode Island Hospital
      • Providence, Rhode Island, Forente stater, 02906
        • Miriam Hospital
    • Vermont
      • Berlin, Vermont, Forente stater, 05602
        • Central Vermont Medical Center/National Life Cancer Treatment
      • Burlington, Vermont, Forente stater, 05405
        • University of Vermont College of Medicine

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

15 år til 59 år (Barn, Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Unequivocal histologic diagnosis of AML (> 20% blasts in the bone marrow based on the World Health Organization [WHO] and/or French American British [FAB] classifications), excluding M3 (acute promyelocytic leukemia); patients with antecedent myelodysplasia are eligible for treatment on this trial only if there were no bone marrow biopsy showing myelodysplastic syndrome (MDS) > 3 months prior to enrollment; patients with therapy-related AML are eligible if they have been free of their primary disease and have not received any chemotherapy for at least 2 years
  • No prior 5-azacitidine or decitabine therapy

  • No prior treatment for leukemia or myelodysplastic syndrome with four permissible exceptions:

    • Emergency leukapheresis
    • Emergency treatment for hyperleukocytosis with hydroxyurea
    • Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
    • Growth factor/cytokine support

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 or bone marrow transplantation)
See Detailed Description.
Annen: Laboratoriebiomarkøranalyse
Korrelative studier
Legemiddel: Etoposid
Gitt IV
Andre navn:
  • Demetyl Epipodofyllotoksin Ethylidin Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
Legemiddel: Decitabin
Gitt IV
Andre navn:
  • 5-Aza-2'-deoksycytidin
  • Dacogen
  • Decitabin til injeksjon
  • Deoksyazacytidin
  • Dezocitidin
  • Aza-TdC
Annen: Farmakologisk studie
Korrelative studier
Legemiddel: Cytarabin
Gitt IV
Andre navn:
  • P-Cytosin-arabinosid
  • 1-P-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinon
  • 1-B-D-Arabinofuranosylcytosin
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinon
  • 1-Beta-D-arabinofuranosylcytosin
  • 1P-D-Arabinofuranosylcytosin
  • 2(1H)-pyrimidinon, 4-amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-pyrimidinon, 4-amino-lß-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-celle
  • Arabine
  • Arabinofuranosylcytosin
  • Arabinosylcytosin
  • Aracytidin
  • Aracytin
  • Aracytine
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosin Arabinoside
  • Cytosin-p-arabinosid
  • Cytosin-beta-arabinosid
  • Erpalfa
  • Starasid
  • Tarabin PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Beta-cytosin Arabinoside
Legemiddel: Daunorubicin hydroklorid
Gitt IV
Andre navn:
  • Cerubidin
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunomycin hydroklorid
  • Daunomycin, hydroklorid
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin hydroklorid
  • Rubilem
Biologisk: Filgrastim
Gitt SC
Andre navn:
  • G-CSF
  • r-metHuG-CSF
  • Neupogen
  • Rekombinant metionyl human granulocyttkolonistimulerende faktor
  • rG-CSF
  • Tevagrastim
  • FILGRASTIM, LISENSHOLDER USPSESIFISERT
Legemiddel: Busulfan
Gitt IV
Andre navn:
  • Busulfex
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
  • 1,4-bis[metansulfonoksy]butan
  • BUSS
  • Bussulfam
  • Busulfanum
  • Busulfan
  • CB 2041
  • CB-2041
  • Glyzophrol
  • GT 41
  • GT-41
  • Joacamine
  • Metansulfonsyre tetrametylenester
  • Metansulfonsyre, tetrametylenester
  • Mielucin
  • Misulban
  • Myeleukon
  • Mylecytan
  • Myleran
  • Sulfabutin
  • Tetrametylenbis(metansulfonat)
  • Tetrametylen bis[metansulfonat]
  • WR-19508
Fremgangsmåte: Autologous Bone Marrow Transplantation
Undergo autologous bone marrow transplantation
Andre navn:
  • ABMT
  • Autolog benmargstransplantasjon
  • Autolog margtransplantasjon
Fremgangsmåte: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC transplantation
Andre navn:
  • Autolog hematopoetisk celletransplantasjon
  • autolog stamcelletransplantasjon

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Participants Who Completed Maintenance Decitabine.
Tidsramme: Up to 5 years
To determine feasibility of decitabine maintenance, this outcome measures the number of participants who completed all 8 planned cycles of decitabine maintenance as per protocol.
Up to 5 years
Disease-free Survival (DFS) Rate at 1 Year
Tidsramme: At 1 year

For participants who achieved a complete remission (CR), this is the percentage of participants who were alive and relapse free at 1 year. The 1 year rate, with 95% confidence interval, was estimated using the Kaplan-Meier method

A CR is defined as those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils > 1000 mL and platelets >= 100,000 mL).
At 1 year

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Relationship Between Busulfan Pharmacokinetics (Area Under the Curve) and Relapsed Disease
Tidsramme: At baseline, after 2, 4, and 6 hours after the start of busulfan infusion
Results from busulfan pharmacokinetics will be pooled with those from CALGB 19808.
At baseline, after 2, 4, and 6 hours after the start of busulfan infusion

Samarbeidspartnere og etterforskere

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

Sponsor

National Cancer Institute (NCI)

Etterforskere

  • Hovedetterforsker: William Blum, Alliance for Clinical Trials in Oncology

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

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)

15. november 2006

Primær fullføring (Faktiske)

31. januar 2011

Studiet fullført (Faktiske)

1. desember 2016

Datoer for studieregistrering

Først innsendt

27. desember 2006

Først innsendt som oppfylte QC-kriteriene

27. desember 2006

Først lagt ut (Anslag)

28. desember 2006

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

19. februar 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

29. januar 2019

Sist bekreftet

1. januar 2019

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • NCI-2009-00444 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH-stipend/kontrakt)
  • U10CA031946 (U.S. NIH-stipend/kontrakt)
  • CDR0000521603
  • CALGB 10503 (Annen identifikator: Alliance for Clinical Trials in Oncology)
  • CALGB-10503 (Annen identifikator: CTEP)
  • R21CA128377 (U.S. NIH-stipend/kontrakt)

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. .

Kliniske studier på Akutt myeloid leukemi

Kliniske studier på Laboratoriebiomarkøranalyse

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Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

CROs by country

CROs in Egypt

Forhold

Sjeldne sykdommer

Legemiddelintervensjoner

Kosttilskudd

Sponsor / samarbeidspartnere

Steder

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