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Imatinib Mesylate, Daunorubicin, and Cytarabine in Treating Patients With Relapsed Acute Myeloid Leukemia

12. februar 2013 opdateret af: The Cleveland Clinic

A Phase I Trial of Imatinib Mesylate (Gleevec, Formerly Known as STI571) in Combination With Daunorubicin and Cytarabine for C-kit Positive Relapsed AML

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with daunorubicin and cytarabine may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with daunorubicin and cytarabine in treating patients with relapsed acute myeloid leukemia.

Studieoversigt

Detaljeret beskrivelse

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) and recommended phase II dose of imatinib mesylate in combination with daunorubicin hydrochloride and cytarabine in patients with relapsed acute myeloid leukemia.

Secondary

  • Assess the non-dose-limiting toxicities associated with this regimen in these patients.
  • Determine any preliminary evidence of clinical activity of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of imatinib mesylate.

Patients receive daunorubicin IV on days 1-3 and cytarabine IV continuously on days 1-7. Patients also receive oral imatinib mesylate once daily beginning on day 1 and continuing until disease progression or unacceptable toxicity. Patients with persistent leukemia on day 14 bone marrow biopsy but ≥ 50% reduction in bone marrow blasts receive 5 more days of cytarabine and 2 more days of daunorubicin while continuing imatinib mesylate.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

21

Fase

  • Fase 1

Kontakter og lokationer

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

Studiesteder

    • Ohio
      • Cleveland, Ohio, Forenede Stater, 44195
        • Cleveland Clinic Taussig Cancer Center

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

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • Bone marrow biopsy confirming acute myeloid leukemia (AML)

    • No M3 AML
  • Patient must have relapsed to standard chemotherapy

    • Patients who relapse within six months of response to treatment or those who never responded to an anthracycline/cytarabine combination will be excluded
  • At least 20% of peripheral blood or bone marrow blasts positive for c-kit
  • No evidence of leptomeningeal involvement

PATIENT CHARACTERISTICS:

  • ECOG Performance Status 0-2
  • Liver enzymes (AST and ALT) and total bilirubin ≤ 2 times upper limit of normal
  • Serum creatinine ≤ 2 times upper limit of normal
  • No New York Heart Association grade III or IV cardiac problems

    • Defined as congestive heart failure or myocardial infraction within the past 6 months
  • No known chronic liver disease (i.e., chronic active hepatitis and cirrhosis)
  • No serious or poorly controlled medical conditions that could be exacerbated by the treatment or would seriously complicate compliance with this study
  • No other active primary malignancy unless it is not currently clinically significant and does not require active intervention
  • No history of HIV infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No significant history of noncompliance to medical regimens or inability to grant reliable informed consent

PRIOR CONCURRENT THERAPY:

  • Previous treatment-related toxicities should be resolved
  • No other investigational agents within the past 28 days
  • No chemotherapy within the past 4 weeks

    • 6 weeks for nitrosourea or mitomycin C
  • No major surgery within the past 4 weeks
  • No concurrent use of the following drugs is allowed: ketoconazole, dilantin, itraconazole, erythromycin, clarithromycin, dexamethasone, rifampin, tegretol, phenobarbital, Hypericum perforatum (St. John's wort), cyclosporine, pimozide, warfarin, certain HMG-CoA reductase inhibitors, traizolo-benzodiazepines, or dihydropyridine calcium channel blockers
  • No other concurrent anticancer agents, including chemotherapy and biologic agents
  • No other concurrent investigational drugs
  • Concurrent medications known to be metabolized by cytochrome p450 enzymes are allowed
  • No therapeutic anticoagulation with warfarin will be permitted in patients participating in this study

    • Therapeutic anticoagulation may be accomplished using low-molecular weight heparin
    • Mini-dose warfarin for prophylaxis of central venous catheter thrombosis allowed
  • No concurrent routine use of systemic corticosteroid therapy

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)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Maximum tolerated dose of imatinib mesylate at one year
Tidsramme: 1 year
1 year

Sekundære resultatmål

Resultatmål
Tidsramme
Non-dose limiting toxicities associated with imatinib mesylate at one year
Tidsramme: 1 year
1 year

Samarbejdspartnere og efterforskere

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

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. juli 2003

Primær færdiggørelse (Faktiske)

1. august 2011

Studieafslutning (Faktiske)

1. august 2011

Datoer for studieregistrering

Først indsendt

20. december 2005

Først indsendt, der opfyldte QC-kriterier

20. december 2005

Først opslået (Skøn)

22. december 2005

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

15. februar 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. februar 2013

Sidst verificeret

1. februar 2013

Mere information

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 cytarabine

3
Abonner