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 juni 2019 bijgewerkt door: 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).
Studie Overzicht
Toestand
Voltooid
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
88
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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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, Verenigde Staten, 85724
- (210) University of Arizona Cancer Center
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California
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La Jolla, California, Verenigde Staten, 92093-0960
- (180) University of California, San Diego
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Los Angeles, California, Verenigde Staten, 90048
- (240) Cedars-Sinai Medical Center
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Orange, California, Verenigde Staten, 92868
- (215) Hematology Oncology Medical Group
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Sacramento, California, Verenigde Staten, 95857
- (130) UC Davis Medical Center
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San Luis Obispo, California, Verenigde Staten, 93401
- (200) Coastal Integrative Cancer Care
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Stanford, California, Verenigde Staten, 94305
- (125) University of Stanford
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Colorado
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Aurora, Colorado, Verenigde Staten, 80045
- (115) University of Colorado Anschultz Cancer Center
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Florida
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Miami Beach, Florida, Verenigde Staten, 33140
- (145) Mount Sinai Comprehensive Cancer Center
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Illinois
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Chicago, Illinois, Verenigde Staten, 60612
- (140) Rush University Medical Center
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Kansas
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Westwood, Kansas, Verenigde Staten, 66205
- (185) The University of Kansas Cancer Center
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Kentucky
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Louisville, Kentucky, Verenigde Staten, 40202
- (175) University Lousiville
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Louisiana
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New Orleans, Louisiana, Verenigde Staten, 70072
- (195) Tulane University Hospital Tulane Cancer Center
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Minnesota
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Minneapolis, Minnesota, Verenigde Staten, 55455
- (235) University of Minnesota
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Missouri
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Saint Louis, Missouri, Verenigde Staten, 63110-1093
- (100) Washington University School of Medicine
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Montana
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Billings, Montana, Verenigde Staten, 59101
- (150) Billings Clinic
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New York
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New York, New York, Verenigde Staten, 10029-65749
- (165) Mount Sinai Medical Center New York
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Pennsylvania
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Pittsburgh, Pennsylvania, Verenigde Staten, 15224-1791
- (160) The Western Pennsylvania Hospital- Cancer Institute
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South Carolina
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Greenville, South Carolina, Verenigde Staten, 29605
- (205) Greenville Hospital System
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South Dakota
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Sioux Falls, South Dakota, Verenigde Staten, 57105
- (120) Avera Cancer Institute
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Tennessee
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Nashville, Tennessee, Verenigde Staten, 37203
- (230) Tennessee Oncology, PLLC
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Texas
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Dallas, Texas, Verenigde Staten, 75390-9179
- (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center
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San Antonio, Texas, Verenigde Staten, 78229
- (155) Cancer Care Centers of South Texas
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Wisconsin
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Madison, Wisconsin, Verenigde Staten, 53792
- (135) University of Wisconsin
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
65 jaar en ouder (Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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
Andere namen:
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
Andere namen:
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 |
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Experimenteel: 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
Andere namen:
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 |
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Experimenteel: 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
Andere namen:
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 |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Kaplan Meier Estimates for One Year Survival
Tijdsspanne: 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
Tijdsspanne: 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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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
Tijdsspanne: Complete Response or Morphologic Incomplete Response data not analyzed.
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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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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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Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Percentage of Participants Alive at One Year
Tijdsspanne: Up to 12 months
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Defined as the percentage of participants who survived at one year
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Up to 12 months
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Studie directeur: Robert Gale, MD, Celgene
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
27 april 2012
Primaire voltooiing (Werkelijk)
19 mei 2015
Studie voltooiing (Werkelijk)
15 mei 2018
Studieregistratiedata
Eerst ingediend
19 mei 2011
Eerst ingediend dat voldeed aan de QC-criteria
20 mei 2011
Eerst geplaatst (Schatting)
24 mei 2011
Updates van studierecords
Laatste update geplaatst (Werkelijk)
25 juni 2019
Laatste update ingediend die voldeed aan QC-criteria
17 juni 2019
Laatst geverifieerd
1 juni 2019
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata per histologisch type
- Neoplasmata
- Leukemie
- Leukemie, myeloïde
- Leukemie, myeloïde, acuut
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antimetabolieten, antineoplastische
- Antimetabolieten
- Antineoplastische middelen
- Immunologische factoren
- Angiogenese-remmers
- Angiogenese modulerende middelen
- Groei stoffen
- Groeiremmers
- Lenalidomide
- Azacitidine
Andere studie-ID-nummers
- CC-5013-AML-001
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .