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
2019年6月17日 更新者：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).
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
88
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arizona
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Tucson、Arizona、アメリカ、85724
- (210) University of Arizona Cancer Center
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California
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La Jolla、California、アメリカ、92093-0960
- (180) University of California, San Diego
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Los Angeles、California、アメリカ、90048
- (240) Cedars-Sinai Medical Center
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Orange、California、アメリカ、92868
- (215) Hematology Oncology Medical Group
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Sacramento、California、アメリカ、95857
- (130) UC Davis Medical Center
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San Luis Obispo、California、アメリカ、93401
- (200) Coastal Integrative Cancer Care
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Stanford、California、アメリカ、94305
- (125) University of Stanford
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Colorado
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Aurora、Colorado、アメリカ、80045
- (115) University of Colorado Anschultz Cancer Center
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Florida
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Miami Beach、Florida、アメリカ、33140
- (145) Mount Sinai Comprehensive Cancer Center
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Illinois
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Chicago、Illinois、アメリカ、60612
- (140) Rush University Medical Center
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Kansas
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Westwood、Kansas、アメリカ、66205
- (185) The University of Kansas Cancer Center
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Kentucky
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Louisville、Kentucky、アメリカ、40202
- (175) University Lousiville
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Louisiana
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New Orleans、Louisiana、アメリカ、70072
- (195) Tulane University Hospital Tulane Cancer Center
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Minnesota
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Minneapolis、Minnesota、アメリカ、55455
- (235) University of Minnesota
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Missouri
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Saint Louis、Missouri、アメリカ、63110-1093
- (100) Washington University School of Medicine
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Montana
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Billings、Montana、アメリカ、59101
- (150) Billings Clinic
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New York
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New York、New York、アメリカ、10029-65749
- (165) Mount Sinai Medical Center New York
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15224-1791
- (160) The Western Pennsylvania Hospital- Cancer Institute
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South Carolina
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Greenville、South Carolina、アメリカ、29605
- (205) Greenville Hospital System
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South Dakota
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Sioux Falls、South Dakota、アメリカ、57105
- (120) Avera Cancer Institute
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- (230) Tennessee Oncology, PLLC
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Texas
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Dallas、Texas、アメリカ、75390-9179
- (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center
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San Antonio、Texas、アメリカ、78229
- (155) Cancer Care Centers of South Texas
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
- (135) University of Wisconsin
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Alberta
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Calgary、Alberta、カナダ、T2N 4N2
- (402) Tom Baker Cancer Centre
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Edmonton、Alberta、カナダ、T6G 1Z1
- (405) University of Alberta Hospital
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Manitoba
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Winnipeg、Manitoba、カナダ、R3E 0V9
- (401) Cancer Care Manitoba
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Nova Scotia
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Halifax、Nova Scotia、カナダ、B3H 2Y9
- (403) Queen Elizabeth II Health Sciences Centre - VG Site
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Ontario
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Ottawa、Ontario、カナダ、K1H 8L6
- (404) The Ottawa Hospital
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Toronto、Ontario、カナダ、M5G 2M9
- (400) Princess Margaret Hospital
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
65年歳以上 (高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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
他の名前：
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
他の名前：
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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実験的：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
他の名前：
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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実験的：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
他の名前：
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 |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Kaplan Meier Estimates for One Year Survival
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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.
|
Overall response rate time frame was not analyzed.
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Progression-Free Survival (PFS)
時間枠：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)
時間枠：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.
|
Event-Free survival time was not analyzed.
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Relapse-Free Survival (RFS)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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.
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From randomization of the last participant up to a minimum of 4 years following discontinuation
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage of Participants Alive at One Year
時間枠：Up to 12 months
|
Defined as the percentage of participants who survived at one year
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Up to 12 months
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Robert Gale, MD、Celgene
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2012年4月27日
一次修了 (実際)
2015年5月19日
研究の完了 (実際)
2018年5月15日
試験登録日
最初に提出
2011年5月19日
QC基準を満たした最初の提出物
2011年5月20日
最初の投稿 (見積もり)
2011年5月24日
学習記録の更新
投稿された最後の更新 (実際)
2019年6月25日
QC基準を満たした最後の更新が送信されました
2019年6月17日
最終確認日
2019年6月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。