- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00416598
Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia
Phase II Study of Maintenance Therapy With Decitabine (NSC #127716) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years
Aperçu de l'étude
Statut
Les conditions
- Leucémie myéloïde aiguë
- Leucémie myéloïde aiguë non traitée chez l'adulte
- Leucémie myéloïde aiguë de l'adulte avec Inv(16)(p13.1q22); CBFB-MYH11
- Leucémie myéloïde aiguë de l'adulte avec t(16;16)(p13.1;q22); CBFB-MYH11
- Leucémie myéloïde aiguë de l'adulte avec t(8;21); (q22 ; q22.1 ); RUNX1-RUNX1T1
- Leucémie myéloïde aiguë de l'adulte avec t(9;11)(p22.3;q23.3); MLLT3-KMT2A
- Leucémie myéloïde aiguë avec modifications liées à la myélodysplasie
Intervention / Traitement
- Autre: Analyse de biomarqueurs en laboratoire
- Médicament: Étoposide
- Médicament: Décitabine
- Autre: Étude pharmacologique
- Médicament: Cytarabine
- Médicament: Chlorhydrate de daunorubicine
- Biologique: Filgrastim
- Médicament: Busulfan
- Procédure: Autologous Bone Marrow Transplantation
- Procédure: Autologous Hematopoietic Stem Cell Transplantation
Description détaillée
PRIMARY OBJECTIVES:
I. To determine the efficacy, feasibility, and toxicities when one year of maintenance therapy with decitabine is given to patients < 60 years with untreated acute myeloid leukemia (AML) who achieve and maintain first complete remission (CR) following an established induction and intensification regimen.
II. To determine the 1-year disease free survival rate for AML patients in first CR treated with maintenance decitabine.
SECONDARY OBJECTIVES:
I. To measure biologic response to decitabine in evaluable patients with fusion genes to determine eradication of minimal residual disease.
II. To measure surrogates for deoxyribonucleic acid (DNA) demethylation including downregulation of DNA methyltransferase 1 (DNMT1) and induction of fetal hemoglobin.
III. To examine the significance of gene re expression following ex vivo decitabine exposure in primary AML cells taken at the time of diagnosis on clinical outcome and on gene expression at the time of relapse after in vivo decitabine exposure.
IV. To continue to evaluate the effectiveness of a cytogenetically risk-adapted approach for consolidation therapy for patients with core binding factor (CBF) or non-CBF AML.
V. To continue the investigation begun in Cancer and Leukemia Group B (CALGB) 19808 aimed at correlation of the rate of relapse and toxicity with intravenous (IV) busulfan pharmacokinetics when busulfan and etoposide are used as the preparative regimen for autologous stem cell transplantation for AML patients in first CR.
VI. To correlate outcome measures such as complete response (CR), disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), with pretreatment characteristics such as age, sex, race, blood counts, morphology, immunophenotype, cytogenetics, and molecular features of AML.
OUTLINE:
REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 168 hours on days 1-7 and daunorubicin hydrochloride IV over 5-10 minutes and etoposide IV over 2 hours on days 1-3. Patients undergo bone marrow biopsy on day 14. Patients with residual leukemia proceed to second remission induction therapy. Patients achieving complete remission (CR) proceed to intensification therapy.
SECOND REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 120 hours on days 1-5 and daunorubicin hydrochloride IV and etoposide IV over 2 hours on days 1 and 2. Patients undergo bone marrow biopsy on day 42. Patients with residual leukemia are removed from the study. Patients achieving CR proceed to intensification therapy.
INTENSIFICATION THERAPY: Patients are stratified and receive intensification therapy according to cytogenetic findings (favorable cytogenetics [t(8;21)(q22q22), inv(16)(p13;q22), or t(16;16)(p13;q22) by cytogenetic and/or molecular analysis] vs unfavorable cytogenetics [all other cytogenetic findings, including normal cytogenetics]).
FAVORABLE CYTOGENETICS: Within 2-4 weeks after achieving CR, patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5.
Treatment repeats every 28 days for up to 3 courses.
UNFAVORABLE CYTOGENETICS: Peripheral blood stem cell (PBSC) mobilization: Within 2-4 weeks after achieving CR, patients receive etoposide IV over 96 hours and high-dose cytarabine IV over 2 hours twice daily on days 1-4 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 14 and continuing until blood counts recover. Patients then proceed to transplantation.
PBSC OR BONE MARROW TRANSPLANTATION: Patients receive busulfan IV over 2 hours 4 times daily on days -7 to -4 and etoposide IV over 4 hours on day -3. Patients undergo autologous PBSC or bone marrow transplantation on day 0 and receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.
UNFAVORABLE CYTOGENETICS AND UNABLE TO UNDERGO PBSC TRANSPLANTATION: Within 2-4 weeks after achieving CR, patients receive etoposide, high-dose cytarabine, and G-CSF as in unfavorable cytogenetics (PBSC mobilization) followed by 2 courses of high-dose cytarabine as in favorable genetics.
MAINTENANCE THERAPY: Within 60-90 days after completion of intensification therapy, patients receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 6 weeks for up to 8 courses.
After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 2 years, and then yearly for 2 years.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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California
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San Francisco, California, États-Unis, 94115
- UCSF Medical Center-Mount Zion
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Delaware
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Lewes, Delaware, États-Unis, 19958
- Beebe Medical Center
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Newark, Delaware, États-Unis, 19718
- Christiana Care Health System-Christiana Hospital
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Florida
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Orlando, Florida, États-Unis, 32803
- Florida Hospital Orlando
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Georgia
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Atlanta, Georgia, États-Unis, 30342
- Blood and Marrow Transplant Group of Georgia
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Illinois
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Chicago, Illinois, États-Unis, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, États-Unis, 60612
- University of Illinois
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Evanston, Illinois, États-Unis, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Indiana
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Fort Wayne, Indiana, États-Unis, 46845
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
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Iowa
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Iowa City, Iowa, États-Unis, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Bangor, Maine, États-Unis, 04401
- Eastern Maine Medical Center
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Maryland
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Baltimore, Maryland, États-Unis, 21201
- University of Maryland/Greenebaum Cancer Center
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Bethesda, Maryland, États-Unis, 20889-5600
- Walter Reed National Military Medical Center
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Elkton, Maryland, États-Unis, 21921
- Union Hospital of Cecil County
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Massachusetts
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Boston, Massachusetts, États-Unis, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, États-Unis, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, États-Unis, 02114
- Massachusetts General Hospital Cancer Center
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Worcester, Massachusetts, États-Unis, 01605
- Commonwealth Hematology Oncology PC-Worcester
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Missouri
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Columbia, Missouri, États-Unis, 65212
- University of Missouri - Ellis Fischel
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Columbia, Missouri, États-Unis, 65201
- Veterans Administration
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Saint Louis, Missouri, États-Unis, 63110
- Washington University School of Medicine
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Nebraska
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North Platte, Nebraska, États-Unis, 69101
- Great Plains Health Callahan Cancer Center
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Omaha, Nebraska, États-Unis, 68198
- University Of Nebraska Medical Center
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Nevada
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Las Vegas, Nevada, États-Unis, 89109
- Sunrise Hospital and Medical Center
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Las Vegas, Nevada, États-Unis, 89102
- University Medical Center of Southern Nevada
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Las Vegas, Nevada, États-Unis, 89106
- Nevada Cancer Research Foundation CCOP
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New Hampshire
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Keene, New Hampshire, États-Unis, 03431
- Cheshire Medical Center-Dartmouth-Hitchcock Keene
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Lebanon, New Hampshire, États-Unis, 03756
- Dartmouth Hitchcock Medical Center
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New Jersey
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Camden, New Jersey, États-Unis, 08103
- Cooper Hospital University Medical Center
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New York
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Buffalo, New York, États-Unis, 14263
- Roswell Park Cancer Institute
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Lake Success, New York, États-Unis, 11042
- Northwell Health NCORP
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Lake Success, New York, États-Unis, 11042
- Northwell Health/Center for Advanced Medicine
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Manhasset, New York, États-Unis, 11030
- North Shore University Hospital
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New Hyde Park, New York, États-Unis, 11040
- Long Island Jewish Medical Center
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New York, New York, États-Unis, 10029
- Mount Sinai Hospital
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Syracuse, New York, États-Unis, 13210
- State University of New York Upstate Medical University
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North Carolina
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Chapel Hill, North Carolina, États-Unis, 27599
- UNC Lineberger Comprehensive Cancer Center
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Goldsboro, North Carolina, États-Unis, 27534
- Wayne Memorial Hospital
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Winston-Salem, North Carolina, États-Unis, 27157
- Wake Forest University Health Sciences
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Ohio
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Columbus, Ohio, États-Unis, 43210
- Ohio State University Comprehensive Cancer Center
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Pittsburgh, Pennsylvania, États-Unis, 15224
- West Penn Hospital
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Rhode Island
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Providence, Rhode Island, États-Unis, 02903
- Rhode Island Hospital
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Providence, Rhode Island, États-Unis, 02906
- Miriam Hospital
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Vermont
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Berlin, Vermont, États-Unis, 05602
- Central Vermont Medical Center/National Life Cancer Treatment
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Burlington, Vermont, États-Unis, 05405
- University of Vermont College of Medicine
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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
Inclusion Criteria:
- Unequivocal histologic diagnosis of AML (> 20% blasts in the bone marrow based on the World Health Organization [WHO] and/or French American British [FAB] classifications), excluding M3 (acute promyelocytic leukemia); patients with antecedent myelodysplasia are eligible for treatment on this trial only if there were no bone marrow biopsy showing myelodysplastic syndrome (MDS) > 3 months prior to enrollment; patients with therapy-related AML are eligible if they have been free of their primary disease and have not received any chemotherapy for at least 2 years
- No prior 5-azacitidine or decitabine therapy
No prior treatment for leukemia or myelodysplastic syndrome with four permissible exceptions:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea
- Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
- Growth factor/cytokine support
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 |
---|---|
Expérimental: Treatment (chemotherapy, PBSC or bone marrow transplantation)
See Detailed Description.
|
Études corrélatives
Étant donné IV
Autres noms:
Étant donné IV
Autres noms:
Études corrélatives
Étant donné IV
Autres noms:
Étant donné IV
Autres noms:
Étant donné SC
Autres noms:
Étant donné IV
Autres noms:
Undergo autologous bone marrow transplantation
Autres noms:
Undergo autologous PBSC transplantation
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Number of Participants Who Completed Maintenance Decitabine.
Délai: Up to 5 years
|
To determine feasibility of decitabine maintenance, this outcome measures the number of participants who completed all 8 planned cycles of decitabine maintenance as per protocol.
|
Up to 5 years
|
Disease-free Survival (DFS) Rate at 1 Year
Délai: At 1 year
|
For participants who achieved a complete remission (CR), this is the percentage of participants who were alive and relapse free at 1 year. The 1 year rate, with 95% confidence interval, was estimated using the Kaplan-Meier method A CR is defined as those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils > 1000 mL and platelets >= 100,000 mL). |
At 1 year
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Relationship Between Busulfan Pharmacokinetics (Area Under the Curve) and Relapsed Disease
Délai: At baseline, after 2, 4, and 6 hours after the start of busulfan infusion
|
Results from busulfan pharmacokinetics will be pooled with those from CALGB 19808.
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At baseline, after 2, 4, and 6 hours after the start of busulfan infusion
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: William Blum, Alliance for Clinical Trials in Oncology
Publications et liens utiles
Publications générales
- Yin J, LaPlant B, Uy GL, Marcucci G, Blum W, Larson RA, Stone RM, Mandrekar SJ. Evaluation of event-free survival as a robust end point in untreated acute myeloid leukemia (Alliance A151614). Blood Adv. 2019 Jun 11;3(11):1714-1721. doi: 10.1182/bloodadvances.2018026112.
- Blum W, Sanford BL, Klisovic R, DeAngelo DJ, Uy G, Powell BL, Stock W, Baer MR, Kolitz JE, Wang ES, Hoke E, Mrozek K, Kohlschmidt J, Bloomfield CD, Geyer S, Marcucci G, Stone RM, Larson RA; Alliance for Clinical Trials in Oncology. Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503). Leukemia. 2017 Jan;31(1):34-39. doi: 10.1038/leu.2016.252. Epub 2016 Sep 13.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
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 (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Leucémie
- Leucémie myéloïde
- Leucémie, myéloïde, aiguë
- 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
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Agents antinéoplasiques phytogéniques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Agents dermatologiques
- Adjuvants, immunologique
- Antibiotiques, Antinéoplasiques
- Agents kératolytiques
- Étoposide
- Phosphate d'étoposide
- Décitabine
- Podophyllotoxine
- Lénograstim
- Cytarabine
- Daunorubicine
- Busulfan
Autres numéros d'identification d'étude
- NCI-2009-00444 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- U10CA180821 (Subvention/contrat des NIH des États-Unis)
- U10CA031946 (Subvention/contrat des NIH des États-Unis)
- CDR0000521603
- CALGB 10503 (Autre identifiant: Alliance for Clinical Trials in Oncology)
- CALGB-10503 (Autre identifiant: CTEP)
- R21CA128377 (Subvention/contrat des NIH des États-Unis)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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