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 uppdaterad av: 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).
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
88
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
Arizona
-
Tucson, Arizona, Förenta staterna, 85724
- (210) University of Arizona Cancer Center
-
-
California
-
La Jolla, California, Förenta staterna, 92093-0960
- (180) University of California, San Diego
-
Los Angeles, California, Förenta staterna, 90048
- (240) Cedars-Sinai Medical Center
-
Orange, California, Förenta staterna, 92868
- (215) Hematology Oncology Medical Group
-
Sacramento, California, Förenta staterna, 95857
- (130) UC Davis Medical Center
-
San Luis Obispo, California, Förenta staterna, 93401
- (200) Coastal Integrative Cancer Care
-
Stanford, California, Förenta staterna, 94305
- (125) University of Stanford
-
-
Colorado
-
Aurora, Colorado, Förenta staterna, 80045
- (115) University of Colorado Anschultz Cancer Center
-
-
Florida
-
Miami Beach, Florida, Förenta staterna, 33140
- (145) Mount Sinai Comprehensive Cancer Center
-
-
Illinois
-
Chicago, Illinois, Förenta staterna, 60612
- (140) Rush University Medical Center
-
-
Kansas
-
Westwood, Kansas, Förenta staterna, 66205
- (185) The University of Kansas Cancer Center
-
-
Kentucky
-
Louisville, Kentucky, Förenta staterna, 40202
- (175) University Lousiville
-
-
Louisiana
-
New Orleans, Louisiana, Förenta staterna, 70072
- (195) Tulane University Hospital Tulane Cancer Center
-
-
Minnesota
-
Minneapolis, Minnesota, Förenta staterna, 55455
- (235) University of Minnesota
-
-
Missouri
-
Saint Louis, Missouri, Förenta staterna, 63110-1093
- (100) Washington University School of Medicine
-
-
Montana
-
Billings, Montana, Förenta staterna, 59101
- (150) Billings Clinic
-
-
New York
-
New York, New York, Förenta staterna, 10029-65749
- (165) Mount Sinai Medical Center New York
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Förenta staterna, 15224-1791
- (160) The Western Pennsylvania Hospital- Cancer Institute
-
-
South Carolina
-
Greenville, South Carolina, Förenta staterna, 29605
- (205) Greenville Hospital System
-
-
South Dakota
-
Sioux Falls, South Dakota, Förenta staterna, 57105
- (120) Avera Cancer Institute
-
-
Tennessee
-
Nashville, Tennessee, Förenta staterna, 37203
- (230) Tennessee Oncology, PLLC
-
-
Texas
-
Dallas, Texas, Förenta staterna, 75390-9179
- (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center
-
San Antonio, Texas, Förenta staterna, 78229
- (155) Cancer Care Centers of South Texas
-
-
Wisconsin
-
Madison, Wisconsin, Förenta staterna, 53792
- (135) University of Wisconsin
-
-
-
-
Alberta
-
Calgary, Alberta, Kanada, T2N 4N2
- (402) Tom Baker Cancer Centre
-
Edmonton, Alberta, Kanada, T6G 1Z1
- (405) University of Alberta Hospital
-
-
Manitoba
-
Winnipeg, Manitoba, Kanada, R3E 0V9
- (401) Cancer Care Manitoba
-
-
Nova Scotia
-
Halifax, Nova Scotia, Kanada, B3H 2Y9
- (403) Queen Elizabeth II Health Sciences Centre - VG Site
-
-
Ontario
-
Ottawa, Ontario, Kanada, K1H 8L6
- (404) The Ottawa Hospital
-
Toronto, Ontario, Kanada, M5G 2M9
- (400) Princess Margaret Hospital
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
65 år och äldre (Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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
|
Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Andra namn:
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
Andra namn:
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 |
|
Experimentell: 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
|
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
Andra namn:
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 |
|
Experimentell: 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
|
Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Andra namn:
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 |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Kaplan Meier Estimates for One Year Survival
Tidsram: Up to 24 months
|
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
|
Up to 24 months
|
|
Overall Survival
Tidsram: 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)
|
Overall Survival reported at the end of the study are for those participants who were alive at the end of the study
|
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)
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
Tidsram: 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.
|
|
Duration of Remission (DoR)
Tidsram: Duration of Remission (DoR) time frame not analyzed.
|
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.
|
Duration of Remission (DoR) time frame not analyzed.
|
|
Cytogenetic Complete Remission Rate (CRc)
Tidsram: Cytogenetic Complete Remission timeframe was not analyzed.
|
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.
|
Cytogenetic Complete Remission timeframe was not analyzed.
|
|
Percentage of Participants With an Overall Response Rate (CR +CRi+ PR)
Tidsram: Overall response rate time frame was not analyzed.
|
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.
|
Overall response rate time frame was not analyzed.
|
|
Progression-Free Survival (PFS)
Tidsram: Progression-Free survival data and time frame was not analyzed.
|
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.
|
Progression-Free survival data and time frame was not analyzed.
|
|
Event-Free Survival (EFS)
Tidsram: Event-Free survival time was not analyzed.
|
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.
|
Event-Free survival time was not analyzed.
|
|
Relapse-Free Survival (RFS)
Tidsram: Relapse-Free survival time frame was not analyzed.
|
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.
|
Relapse-Free survival time frame was not analyzed.
|
|
Percentage of Participants With 30-Day Treatment-Related Mortality
Tidsram: 30 days
|
30-day mortality rate was defined as death from any cause within 30 days after first dose.
|
30 days
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Tidsram: From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
|
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
|
From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
|
|
Number of Participants With a Second Primary Malignancy
Tidsram: From randomization of the last participant up to a minimum of 4 years following discontinuation
|
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.
|
From randomization of the last participant up to a minimum of 4 years following discontinuation
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Percentage of Participants Alive at One Year
Tidsram: Up to 12 months
|
Defined as the percentage of participants who survived at one year
|
Up to 12 months
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Studierektor: Robert Gale, MD, Celgene
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
27 april 2012
Primärt slutförande (Faktisk)
19 maj 2015
Avslutad studie (Faktisk)
15 maj 2018
Studieregistreringsdatum
Först inskickad
19 maj 2011
Först inskickad som uppfyllde QC-kriterierna
20 maj 2011
Första postat (Uppskatta)
24 maj 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
25 juni 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
17 juni 2019
Senast verifierad
1 juni 2019
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Neoplasmer efter histologisk typ
- Neoplasmer
- Leukemi
- Leukemi, myeloid
- Leukemi, Myeloid, Akut
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antimetaboliter, antineoplastiska
- Antimetaboliter
- Antineoplastiska medel
- Immunologiska faktorer
- Angiogeneshämmare
- Angiogenesmodulerande medel
- Tillväxtämnen
- Tillväxthämmare
- Lenalidomid
- Azacitidin
Andra studie-ID-nummer
- CC-5013-AML-001
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .