- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00005793
A Phase I/II Study of Induction Chemotherapy With Daunorubicin, Cytarabine, Topotecan and Etoposide
A Phase I/II Study of Induction Chemotherapy With Daunorubicin, Cytarabine, Topotecan and Etoposide (DATE) for De Novo AML: In the Treatment of Young Patients Ages 16-59
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have previously untreated acute myeloid leukemia.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of topotecan when combined with daunorubicin, cytarabine, and etoposide in patients with de novo acute myeloid leukemia.
- Determine the efficacy of this regimen at the MTD of topotecan by measuring the complete response rate in this patient population.
- Determine the days of hospitalization and number of infections associated with this regimen in these patients.
- Correlate serum levels of topotecan and etoposide with the expression of topoisomerase I and II in tumor cells and in peripheral blood mononuclear cells (PBMN), as well as with toxicity and response rate in these patients.
- Correlate tumor cell and PBMN expression and activity of topoisomerase I and II with hematological toxicity and clinical response in these patients.
- Correlate levels of activation of STAT signaling proteins with expression of bcl-2 family proteins and response to chemotherapy in these patients.
OUTLINE: This is a dose-escalation study of topotecan (phase I) followed by a response rate-determination (phase II) study.
Patients receive induction chemotherapy with daunorubicin IV over 10-15 minutes on days 1-3, cytarabine IV continuously on days 1-5, topotecan IV continuously on days 6-8, and etoposide IV over 60 minutes on days 9 and 10. Within 4 weeks of hematologic recovery, patients achieving remission after induction receive consolidation chemotherapy with cytarabine IV over 1 hour every 12 hours on days 1, 3, and 5. Subsequent courses of consolidation chemotherapy begin within 2 weeks of documentation of hematologic recovery from the prior consolidation course. Consolidation chemotherapy continues for 4 courses in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive induction chemotherapy at the recommended phase II dose.
Patients are followed at 1 month, every 2 months for 1 year, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 3-36 patients (phase I) and then an additional 24-27 patients (phase II) will be accrued for this study within 4 years.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
Florida
-
Tampa, Florida, Forenede Stater, 33612-9497
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
DISEASE CHARACTERISTICS:
Histologically confirmed newly diagnosed, previously untreated acute myeloid leukemia (AML)
- All FAB types, M0-M7, excluding M3
- No AML after myelodysplastic syndrome
PATIENT CHARACTERISTICS:
Age:
- 16 to 59
Performance status:
- Eastern Cooperative Oncology Group (ECOG) 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin less than 2 mg/dL
- SGOT/SGPT normal unless due to leukemic disease
- Alkaline phosphatase normal unless due to leukemic disease
Renal:
- Creatinine no greater than 2.0 mg/dL OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- Ejection fraction at least 50% by MUGA
- No myocardial infarction or serious ventricular arrhythmia within the past 6 months
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other prior malignancy within the past 5 years except resected skin cancer
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior topotecan or any other DNA topoisomerase I inhibitor (e.g., irinotecan, aminocamptothecin, or nitrocamptothecin) or etoposide for any prior malignancy
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Studieplan
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: Combination Chemotherapy
Patients receive induction chemotherapy with daunorubicin IV over 10-15 minutes on days 1-3, cytarabine IV continuously on days 1-5, topotecan IV continuously on days 6-8, and etoposide IV over 60 minutes on days 9 and 10.
Within 4 weeks of hematologic recovery, patients achieving remission after induction receive consolidation chemotherapy with cytarabine IV over 1 hour every 12 hours on days 1, 3, and 5. Subsequent courses of consolidation chemotherapy begin within 2 weeks of documentation of hematologic recovery from the prior consolidation course.
Consolidation chemotherapy continues for 4 courses in the absence of unacceptable toxicity or disease progression.
|
Andre navne:
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Maximum Tolerated Dose (MTD)
Tidsramme: 2 years
|
Determine the maximum tolerated dose (MTD) of topotecan when combined with daunorubicin, cytarabine, and etoposide in patients with de novo acute myeloid leukemia.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
|
2 years
|
Samarbejdspartnere og efterforskere
Efterforskere
- Studiestol: Hussain I. Saba, MD, PhD, H. Lee Moffitt Cancer Center and Research Institute
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- akut myeloid leukæmi hos voksne med 11q23 (MLL) abnormiteter
- akut myeloid leukæmi hos voksne med inv(16)(p13;q22)
- akut myeloid leukæmi hos voksne med t(16;16)(p13;q22)
- akut myeloid leukæmi hos voksne med t(8;21)(q22;q22)
- ubehandlet akut myeloid leukæmi hos voksne
- akut erythroid leukæmi hos voksne (M6)
- akut megakaryoblastisk leukæmi hos voksne (M7)
- voksen akut minimalt differentieret myeloid leukæmi (M0)
- akut monoblastisk leukæmi hos voksne (M5a)
- akut monocytisk leukæmi hos voksne (M5b)
- akut myeloblastisk leukæmi hos voksne med modning (M2)
- voksen akut myeloblastisk leukæmi uden modning (M1)
- akut myelomonocytisk leukæmi hos voksne (M4)
Yderligere relevante MeSH-vilkår
- Neoplasmer efter histologisk type
- Neoplasmer
- Leukæmi
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Antivirale midler
- Enzymhæmmere
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, fytogene
- Topoisomerase II-hæmmere
- Topoisomerasehæmmere
- Antibiotika, antineoplastisk
- Topoisomerase I-hæmmere
- Etoposid
- Cytarabin
- Daunorubicin
- Topotecan
Andre undersøgelses-id-numre
- MCC-11941
- CA 82533 (Anden identifikator: NCI)
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 Topotecan
-
Targeted Therapy Technologies, LLCAktiv, ikke rekrutterende
-
The Hospital for Sick ChildrenRekruttering
-
Hospital JP GarrahanHospital San Juan de Dios, SantiagoAktiv, ikke rekrutterendeUnilateral retinoblastomArgentina
-
Gustave Roussy, Cancer Campus, Grand ParisErasmus Medical Center; Catholic University of the Sacred Heart; St. Anna...AfsluttetNeuroblastom | Faste tumorer | HjernetumorerFrankrig
-
GlaxoSmithKlineAfsluttetLungekræft, småcellerForenede Stater, Holland
-
GlaxoSmithKlineAfsluttetLungekræft, småcellerBulgarien, Ungarn, Den Russiske Føderation, Holland, Ukraine, Det Forenede Kongerige
-
GlaxoSmithKlineAfsluttet
-
GlaxoSmithKlineAfsluttetEndometriecancer | Neoplasmer, endometrieForenede Stater, Canada, Ungarn
-
Gachon University Gil Medical CenterUkendtLungekræft | Refraktær overfor kemoterapiKorea, Republikken
-
GlaxoSmithKlineAfsluttetSmåcellet lungekræft | Lungekræft, småcellerForenede Stater