A Study Being Conducted at Multiple Locations to Compare Safety and Efficacy of Three Different Regimens; (1) High-Dose Lenalidomide; (2) Lenalidomide + Azacitidine; or (3) Azacitidine in Subjects ≥ 65 Years With Newly-Diagnosed Acute Myeloid Leukemia
17 juin 2019 mis à jour par: Celgene
A Phase 2, Multicenter, Randomized, Open-label, Parallel-group Study of a Lenalidomide (Revlimid®) Regimen or a Sequential Azacitidine (Vidaza®) Plus Lenalidomide (Revlimid®) Regimen Versus an Azacitidine (Vidaza®) Regimen for Therapy of Older Subjects With Newly Diagnosed Acute Myeloid Leukemia
The study aim is to compare safety and efficacy of high-dose lenalidomide regimen, sequential azacitidine and lenalidomide and an azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia (AML).
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
On September 11, 2013, randomization into the continuous 50 mg lenalidomide only arm was temporarily suspended based on review of the data from the first 13 participants and a high rate of discontinuation (11/13 participants).
The Data Monitoring Committee assessed the study data on September 20, 2013 and reported no safety concerns.
The high rate of early discontinuation is inconsistent with the treatment duration required for testing the study primary endpoint of survival at one year.
Consequently, Celgene has decided not to reopen the lenalidomide only arm.
Type d'étude
Interventionnel
Inscription (Réel)
88
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Alberta
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Calgary, Alberta, Canada, T2N 4N2
- (402) Tom Baker Cancer Centre
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Edmonton, Alberta, Canada, T6G 1Z1
- (405) University of Alberta Hospital
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
- (401) Cancer Care Manitoba
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
- (403) Queen Elizabeth II Health Sciences Centre - VG Site
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- (404) The Ottawa Hospital
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Toronto, Ontario, Canada, M5G 2M9
- (400) Princess Margaret Hospital
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Arizona
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Tucson, Arizona, États-Unis, 85724
- (210) University of Arizona Cancer Center
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California
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La Jolla, California, États-Unis, 92093-0960
- (180) University of California, San Diego
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Los Angeles, California, États-Unis, 90048
- (240) Cedars-Sinai Medical Center
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Orange, California, États-Unis, 92868
- (215) Hematology Oncology Medical Group
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Sacramento, California, États-Unis, 95857
- (130) UC Davis Medical Center
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San Luis Obispo, California, États-Unis, 93401
- (200) Coastal Integrative Cancer Care
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Stanford, California, États-Unis, 94305
- (125) University of Stanford
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Colorado
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Aurora, Colorado, États-Unis, 80045
- (115) University of Colorado Anschultz Cancer Center
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Florida
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Miami Beach, Florida, États-Unis, 33140
- (145) Mount Sinai Comprehensive Cancer Center
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Illinois
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Chicago, Illinois, États-Unis, 60612
- (140) Rush University Medical Center
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Kansas
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Westwood, Kansas, États-Unis, 66205
- (185) The University of Kansas Cancer Center
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Kentucky
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Louisville, Kentucky, États-Unis, 40202
- (175) University Lousiville
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Louisiana
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New Orleans, Louisiana, États-Unis, 70072
- (195) Tulane University Hospital Tulane Cancer Center
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Minnesota
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Minneapolis, Minnesota, États-Unis, 55455
- (235) University of Minnesota
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Missouri
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Saint Louis, Missouri, États-Unis, 63110-1093
- (100) Washington University School of Medicine
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Montana
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Billings, Montana, États-Unis, 59101
- (150) Billings Clinic
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New York
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New York, New York, États-Unis, 10029-65749
- (165) Mount Sinai Medical Center New York
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Pennsylvania
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Pittsburgh, Pennsylvania, États-Unis, 15224-1791
- (160) The Western Pennsylvania Hospital- Cancer Institute
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South Carolina
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Greenville, South Carolina, États-Unis, 29605
- (205) Greenville Hospital System
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South Dakota
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Sioux Falls, South Dakota, États-Unis, 57105
- (120) Avera Cancer Institute
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Tennessee
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Nashville, Tennessee, États-Unis, 37203
- (230) Tennessee Oncology, PLLC
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Texas
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Dallas, Texas, États-Unis, 75390-9179
- (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center
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San Antonio, Texas, États-Unis, 78229
- (155) Cancer Care Centers of South Texas
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Wisconsin
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Madison, Wisconsin, États-Unis, 53792
- (135) University of Wisconsin
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
65 ans et plus (Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Newly diagnosed acute myeloid leukemia (AML), AML with antecedent hematologic disorder or therapy-related AML
- Male or female subjects aged ≥ 65
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- White blood cell (WBC) count ≤ 10 x 10⁹/L at screening
Exclusion Criteria:
- Previous treatment with azacitidine, decitabine, cytarabine or lenalidomide
- Previous cytotoxic or biologic treatment of any kind for AML or prior use of targeted therapy agents.
- Suspected or proven acute promyelocytic leukemia
- Prior bone marrow or stem cell transplantation
- Candidate for allogeneic bone marrow or stem cell transplantation
- AML antecedent hematologic disorder such as chronic myelogenous leukemia or myeloproliferative neoplasms
- Presence of malignant disease within the previous 12 months with exceptions
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Lenalidomide in combination with azacitidine
Repeated cycles of azacitidine 75 mg/m^2/day subcutaneous (SC) on Days 1-7 and lenalidomide 50 mg/day by mouth (PO) on Days 8-28 followed by a 14-day break plus best supportive care
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Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Autres noms:
Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily
Autres noms:
The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support |
|
Expérimental: Lenalidomide - single agent
Lenalidomide 50 mg PO daily for 28 days for the first 2 cycles and lenalidomide 25 mg daily for 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg daily PO plus best supportive care
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Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily
Autres noms:
The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support |
|
Expérimental: Azacitidine-single agent
Repeated cycles of azacitidine 75mg/m^2/day subcutaneous on Days 1-7 followed by a 21-day break plus best supportive care
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Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Autres noms:
The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Kaplan Meier Estimates for One Year Survival
Délai: Up to 24 months
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One-year survival rate was defined as all deaths within one year from the date of randomization.
All others censored at the at year 1 or date of discontinuation
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Up to 24 months
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Overall Survival
Délai: From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)
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Overall Survival reported at the end of the study are for those participants who were alive at the end of the study
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From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
Délai: Complete Response or Morphologic Incomplete Response data not analyzed.
|
Based on IWG response criteria for AML. Complete remission (CR), morphologic complete remission (CR) was defined as < 5% bone marrow blasts, an absolute neutrophil count ≥ 1 x 10^9/L, platelets ≥100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. Morphologic CR with incomplete blood count recovery (CRi) was defined as a morphologic complete remission but the ANC count may be <1 x 10^9/L and/or the platelet count may be <100 x 10^9/L. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed. |
Complete Response or Morphologic Incomplete Response data not analyzed.
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Duration of Remission (DoR)
Délai: Duration of Remission (DoR) time frame not analyzed.
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Duration of remission was defined as the time from the date of CR or CRi until relapse.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Duration of Remission (DoR) time frame not analyzed.
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Cytogenetic Complete Remission Rate (CRc)
Délai: Cytogenetic Complete Remission timeframe was not analyzed.
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The CRc response category is comprised of the subset of participants who had abnormal cytogenetics at baseline and subsequently achieved CR during treatment in conjunction with a reversion to a normal karyotype.
For the primary definition of CRc, a normal karyotype is defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques.
Cytogenetic complete remission rate (CRc) 1) CR criteria met AND 2) Abnormal karyotype present at baseline AND 3) Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Cytogenetic Complete Remission timeframe was not analyzed.
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Percentage of Participants With an Overall Response Rate (CR +CRi+ PR)
Délai: Overall response rate time frame was not analyzed.
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Morphologic complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a one marrow aspirate with spicules and with at least 200 nucleated cells (there should be no blasts with auer rods) and ANC of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, no transfusions for 1 week prior to each assessment.
No duration of these findings is required for confirmation of this response.
Morphologic complete remission with incomplete blood count recovery was defined as a morphologic complete remission but the ANC may be < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L.
Partial remission was defined as an ANC > 1 x 10^9/L and platelet count ≥ 100 x 10^9/L with a > 50% decrease in the percentage of bone marrow blasts to 5% to 25% (a blast count value of ≤ 5% may also be considered a partial remission if auer rods are present).
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Overall response rate time frame was not analyzed.
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Progression-Free Survival (PFS)
Délai: Progression-Free survival data and time frame was not analyzed.
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PFS is defined as the time from randomization to the first observation of documented disease progression or death from any cause whichever occurred first.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Progression-Free survival data and time frame was not analyzed.
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Event-Free Survival (EFS)
Délai: Event-Free survival time was not analyzed.
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EFS was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after CR or CRi, or death from any cause, whichever occurred first.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Event-Free survival time was not analyzed.
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Relapse-Free Survival (RFS)
Délai: Relapse-Free survival time frame was not analyzed.
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RFS is defined only for subjects that achieve CR and CRi and is measured as the interval from that date to the date of disease relapse, death from any cause, whichever occurs first, censoring at the last visit date for subjects alive in continuous CR/CRi.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Relapse-Free survival time frame was not analyzed.
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Percentage of Participants With 30-Day Treatment-Related Mortality
Délai: 30 days
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30-day mortality rate was defined as death from any cause within 30 days after first dose.
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30 days
|
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Number of Participants With Treatment Emergent Adverse Events (TEAE)
Délai: From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
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TEAEs were defined as those events that started on or after the first day of study drug up until 28 days after the last dose of study drug; Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; constitutes an important medical event.
Severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); and according to the scale: Grade (Gr) 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
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From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
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Number of Participants With a Second Primary Malignancy
Délai: From randomization of the last participant up to a minimum of 4 years following discontinuation
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Second primary malignancies were monitored as events of interest and reported as serious adverse events regardless of the treatment arm the participant was enrolled in.
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From randomization of the last participant up to a minimum of 4 years following discontinuation
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Percentage of Participants Alive at One Year
Délai: Up to 12 months
|
Defined as the percentage of participants who survived at one year
|
Up to 12 months
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: Robert Gale, MD, Celgene
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
27 avril 2012
Achèvement primaire (Réel)
19 mai 2015
Achèvement de l'étude (Réel)
15 mai 2018
Dates d'inscription aux études
Première soumission
19 mai 2011
Première soumission répondant aux critères de contrôle qualité
20 mai 2011
Première publication (Estimation)
24 mai 2011
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
25 juin 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
17 juin 2019
Dernière vérification
1 juin 2019
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
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Facteurs immunologiques
- Inhibiteurs de l'angiogenèse
- Agents modulateurs de l'angiogenèse
- Substances de croissance
- Inhibiteurs de croissance
- Lénalidomide
- Azacitidine
Autres numéros d'identification d'étude
- CC-5013-AML-001
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 .