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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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Florida
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Tampa, Florida, États-Unis, 33612-9497
- H. Lee Moffitt Cancer Center and Research Institute
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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.
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Autres noms:
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Maximum Tolerated Dose (MTD)
Délai: 2 years
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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.
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2 years
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Collaborateurs et enquêteurs
Les enquêteurs
- Chaise d'étude: Hussain I. Saba, MD, PhD, H. Lee Moffitt Cancer Center and Research Institute
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
- leucémie myéloïde aiguë de l'adulte avec anomalies 11q23 (MLL)
- leucémie myéloïde aiguë de l'adulte avec inv(16)(p13;q22)
- leucémie myéloïde aiguë de l'adulte avec t(16;16)(p13;q22)
- leucémie myéloïde aiguë de l'adulte avec t(8;21)(q22;q22)
- leucémie myéloïde aiguë de l'adulte non traitée
- leucémie érythroïde aiguë de l'adulte (M6)
- leucémie aiguë mégacaryoblastique de l'adulte (M7)
- leucémie myéloïde aiguë peu différenciée de l'adulte (M0)
- leucémie aiguë monoblastique de l'adulte (M5a)
- leucémie monocytaire aiguë de l'adulte (M5b)
- leucémie aiguë myéloblastique de l'adulte avec maturation (M2)
- leucémie aiguë myéloblastique de l'adulte sans maturation (M1)
- leucémie aiguë myélomonocytaire de l'adulte (M4)
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Leucémie
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques phytogéniques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Antibiotiques, Antinéoplasiques
- Inhibiteurs de la topoisomérase I
- Étoposide
- Cytarabine
- Daunorubicine
- Topotécan
Autres numéros d'identification d'étude
- MCC-11941
- CA 82533 (Autre identifiant: NCI)
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