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A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes

27. oktober 2016 oppdatert av: Washington University School of Medicine
The primary endpoint of this study is to estimate morphologic complete remission rate. Estimation of response rate is also a secondary objection.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care.

The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.

Studietype

Intervensjonell

Registrering (Faktiske)

25

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
    • Missouri
      • St. Louis, Missouri, Forente stater, 63110
        • Washington University School 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

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria:

    • Symptomatic anemia with either hemoglobin less than 10.0 g/dL or requiring RBC transfusion
    • Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
    • Neutropenia with two or more absolute neutrophil counts less than 1,000 /µL.
  2. ECOG performance status of 0-2.
  3. Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
  4. Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal).
  5. Life expectancy of at least 12 weeks.
  6. Have not received any chemotherapy within 4 weeks of study enrollment and must have recovered from any treatment-related toxicities.
  7. Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.
  8. Sexually active women of childbearing potential must use effective birth control during the trial and for an appropriate period after the trial.
  9. Men must be willing to avoid fathering a new child while receiving therapy with azacitidine.
  10. ≥18 years, no upper age limit
  11. Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous azacitidine alone as a treatment prior to transplantation.

Exclusion Criteria:

  1. Known CNS leukemia.
  2. Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
  3. Known or suspected hypersensitivity to azacitidine or mannitol.
  4. Receiving any other investigational agents within 30 days of first dose of study drug.
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
  6. Known positive serology for HIV.
  7. Had radiotherapy within 14 days prior to study enrollment.
  8. Known presence of hepatic tumors.
  9. <18 years of age
  10. Exclude women who are pregnant or breast feeding.

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: Azacitidine
Azacitidine 75 mg/m2 IV on days 1-5 of each 28 day cycle. Patients that do not respond after two cycles will have the dose increased to 100 mg/m2. Patients who achieve a CR will receive 3 additional 28 day cycles and then begin treatment on days 1-5 of a 56 day cycle. Individuals who demonstrate a loss of response will resume 28 day cycles.
Legemiddel: Azacitidin
Andre navn:
  • Vidaza
  • 5-azacitidin

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Rate of Complete Remission (CR) and Partial Remission (PR)
Tidsramme: After 4 cycles of therapy (up to 112 days after start of treatment)

Defined according to the modified International Working Group (IWG) (2006) response criteria for myelodysplasia:

CR=bone marrow with <5% myeloblasts and 0% peripheral blasts, hemoglobin ≥11g/dL, platelets ≥ 100 x 10^9/L, and neutrophils ≥1.0 x 10^9/L. Residual dysplasia was allowed.

PR= All of the CR criteria if abnormal before treatment except: bone marrow blasts decreased by ≥50% over pretreatment but still >5%.
After 4 cycles of therapy (up to 112 days after start of treatment)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Rate of Hematologic Improvement
Tidsramme: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
International Working Group (IWG) for Myelodysplasia (MDS).
4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
Rate of Transfusion Independence
Tidsramme: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
Rate of Cytogenetic Response
Tidsramme: 2 years after first dose of study drug or until participant is lost to follow-up or dies
2 years after first dose of study drug or until participant is lost to follow-up or dies
Rate of Overall Survival
Tidsramme: 2 years after first dose of study drug or until participant is lost to follow-up or dies
Overall survival is defined as the date of first dose of study drug to the date of death from any cause.
2 years after first dose of study drug or until participant is lost to follow-up or dies
Rate of Relapse After Hematopoietic Stem Cell Transplant in Individuals Treated With 5-azacitidine Prior to Transplant.
Tidsramme: 2 years after first dose of study drug or until participant is lost to follow-up or dies
2 years after first dose of study drug or until participant is lost to follow-up or dies

Samarbeidspartnere og etterforskere

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

Sponsor

Washington University School of Medicine

Publikasjoner og nyttige lenker

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Hjelpsomme linker

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. august 2006

Primær fullføring (Faktiske)

1. august 2008

Studiet fullført (Faktiske)

1. mars 2010

Datoer for studieregistrering

Først innsendt

4. oktober 2006

Først innsendt som oppfylte QC-kriteriene

5. oktober 2006

Først lagt ut (Anslag)

6. oktober 2006

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

12. desember 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

27. oktober 2016

Sist bekreftet

1. oktober 2016

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 06-0585

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