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Augmerosen Plus Fludarabine and Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

31. januar 2013 opdateret af: National Cancer Institute (NCI)

A Phase I Study of G3139 (NSC 683428) in Combination With Salvage Chemotherapy for Treatment of Refractory and Relapsed Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)

Phase I trial to study the effectiveness of augmerosen plus fludarabine and cytarabine in treating patients who have refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Gene therapy such as augmerosen may make cancer cells more sensitive to chemotherapy drugs. Combining more than one drug with augmerosen may kill more cancer cells.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

OBJECTIVES:

I. Determine the maximum tolerated dose of fludarabine and cytarabine when combined with augmerosen (G3139) in patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia and recommend a starting dose for phase II studies.

II. Determine the qualitative and quantitative toxic effects of this regimen in these patients with regard to organ specificity, time course, predictability, and reversibility.

III. Document the therapeutic response in patients treated with this regimen. IV. Measure bcl-2 and related antiapoptotic and proapoptotic proteins in circulating and/or marrow leukemia cells before, during, and after treatment with G3139.

V. Measure WT1 expression in leukemic blasts as a surrogate marker for minimal residual disease and correlate it with bcl-2 and related antiapoptotic and proapoptotic gene expression.

VI. Determine the time required for bcl-2 levels to recover after treatment with this regimen.

VII. Determine if TP53 mutations are present in leukemic blasts and how these mutations may affect expression of BAX, level of treatment induced apoptosis, and clinical endpoints.

VIII. Assess apoptosis in leukemic cells before, during, and after treatment with this regimen.

IX. Determine the pharmacokinetics of fludarabine and cytarabine in patients treated with this regimen.

X. Perform pharmacodynamic studies of fludarabine and cytarabine on the leukemic cells of patients prior to treatment.

OUTLINE: This is a dose-escalation study of fludarabine and cytarabine.

Patients receive augmerosen IV continuously on days 1-10 and filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover. Patients receive fludarabine IV over 30 minutes followed 3.5 hours later by cytarabine IV over 4 hours on days 6-10. Patients who achieve complete response (CR) receive a second course beginning 4 weeks after completion of the first course. Patients who achieve CR and have a matched sibling or unrelated bone marrow donor may undergo allogeneic bone marrow transplantation. Cohorts of 3-6 patients receive escalating doses of fludarabine and cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

24

Fase

  • Fase 1

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Ohio
      • Columbus, Ohio, Forenede Stater, 43210-1240
        • Arthur G. James Cancer Hospital - Ohio State University

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

16 år og ældre (Barn, Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • Histologically proven refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia
  • Marrow cellularity must be at least 20%
  • Must have diagnostic lumbar puncture and treatment with prophylactic intrathecal methotrexate within 1 week prior to entering study
  • No active CNS involvement
  • CNS involvement allowed if no residual leukemic cells are detected in CSF following intrathecal chemotherapy

PATIENT CHARACTERISTICS:

  • Age: 16 and over
  • Performance status: ECOG 0-2
  • Life expectancy: At least 4 weeks

  • Bilirubin no greater than 2 times upper limit of normal(ULN)

    • ALT and AST no greater than 2 times ULN
    • Alkaline phosphatase no greater than 2 times ULN*
    • Unless attributable to malignancy
  • Creatinine no greater than 1.5 mg/dL unless attributable to malignancy
  • No symptomatic congestive heart failure
  • No unstable angina pectoris No or cardiac arrhythmia
  • Resting cardiac ejection fraction no less than 45% unless attributable to malignancy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before and during study
  • No history of allergy to study medications
  • No uncontrolled concurrent illness
  • No active infection
  • No serious medical or psychiatric illness that would preclude informed consent or limit survival to less than 4 weeks

PRIOR CONCURRENT THERAPY:

  • At least 2 weeks since prior chemotherapy except hydroxyurea
  • No concurrent corticosteroids except for grade 4 toxicity unresponsive to all other agents
  • At least 4 weeks since prior radiotherapy
  • No other concurrent investigational or standard agents or therapies for leukemia

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: Arm I
Patients receive augmerosen IV continuously on days 1-10 and filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover. Patients receive fludarabine IV over 30 minutes followed 3.5 hours later by cytarabine IV over 4 hours on days 6-10. Patients who achieve complete response (CR) receive a second course beginning 4 weeks after completion of the first course. Patients who achieve CR and have a matched sibling or unrelated bone marrow donor may undergo allogeneic bone marrow transplantation. Cohorts of 3-6 patients receive escalating doses of fludarabine and cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Medicin: cytarabin
Medicin: fludarabin fosfat
Biologisk: filgrastim
Biologisk: oblimersen natrium

Samarbejdspartnere og efterforskere

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

Sponsor

National Cancer Institute (NCI)

Efterforskere

  • Studiestol: Guido Marcucci, MD, Ohio State University Comprehensive Cancer Center

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. oktober 1999

Primær færdiggørelse (Faktiske)

1. december 2001

Datoer for studieregistrering

Først indsendt

7. marts 2000

Først indsendt, der opfyldte QC-kriterier

28. januar 2004

Først opslået (Skøn)

29. januar 2004

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

1. februar 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

31. januar 2013

Sidst verificeret

1. maj 2002

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NCI-2012-01399
  • OSU-99H0257
  • OSU-9977
  • NCI-T99-0057
  • CDR0000067515 (Registry Identifier: PDQ (Physician Data Query))

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 .

Kliniske forsøg med cytarabin

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Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

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Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

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