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
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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California
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San Francisco、California、アメリカ、94115
- UCSF Medical Center-Mount Zion
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Delaware
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Lewes、Delaware、アメリカ、19958
- Beebe Medical Center
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Newark、Delaware、アメリカ、19718
- Christiana Care Health System-Christiana Hospital
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Florida
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Orlando、Florida、アメリカ、32803
- Florida Hospital Orlando
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Georgia
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Atlanta、Georgia、アメリカ、30342
- Blood and Marrow Transplant Group of Georgia
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Illinois
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Chicago、Illinois、アメリカ、60637
- University of Chicago Comprehensive Cancer Center
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Chicago、Illinois、アメリカ、60612
- University of Illinois
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Evanston、Illinois、アメリカ、60201
- NorthShore University HealthSystem-Evanston Hospital
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Indiana
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Fort Wayne、Indiana、アメリカ、46845
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
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Iowa
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Iowa City、Iowa、アメリカ、52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Bangor、Maine、アメリカ、04401
- Eastern Maine Medical Center
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Maryland
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Baltimore、Maryland、アメリカ、21201
- University of Maryland/Greenebaum Cancer Center
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Bethesda、Maryland、アメリカ、20889-5600
- Walter Reed National Military Medical Center
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Elkton、Maryland、アメリカ、21921
- Union Hospital of Cecil County
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Dana-Farber Cancer Institute
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Boston、Massachusetts、アメリカ、02115
- Brigham and Women's Hospital
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital Cancer Center
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Worcester、Massachusetts、アメリカ、01605
- Commonwealth Hematology Oncology PC-Worcester
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Missouri
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Columbia、Missouri、アメリカ、65212
- University of Missouri - Ellis Fischel
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Columbia、Missouri、アメリカ、65201
- Veterans Administration
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Saint Louis、Missouri、アメリカ、63110
- Washington University School of Medicine
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Nebraska
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North Platte、Nebraska、アメリカ、69101
- Great Plains Health Callahan Cancer Center
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Omaha、Nebraska、アメリカ、68198
- University of Nebraska Medical Center
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Nevada
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Las Vegas、Nevada、アメリカ、89109
- Sunrise Hospital and Medical Center
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Las Vegas、Nevada、アメリカ、89102
- University Medical Center of Southern Nevada
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Las Vegas、Nevada、アメリカ、89106
- Nevada Cancer Research Foundation CCOP
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New Hampshire
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Keene、New Hampshire、アメリカ、03431
- Cheshire Medical Center-Dartmouth-Hitchcock Keene
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Lebanon、New Hampshire、アメリカ、03756
- Dartmouth Hitchcock Medical Center
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New Jersey
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Camden、New Jersey、アメリカ、08103
- Cooper Hospital University Medical Center
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New York
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Buffalo、New York、アメリカ、14263
- Roswell Park Cancer Institute
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Lake Success、New York、アメリカ、11042
- Northwell Health NCORP
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Lake Success、New York、アメリカ、11042
- Northwell Health/Center for Advanced Medicine
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Manhasset、New York、アメリカ、11030
- North Shore University Hospital
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New Hyde Park、New York、アメリカ、11040
- Long Island Jewish Medical Center
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New York、New York、アメリカ、10029
- Mount Sinai Hospital
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Syracuse、New York、アメリカ、13210
- State University of New York Upstate Medical University
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- UNC Lineberger Comprehensive Cancer Center
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Goldsboro、North Carolina、アメリカ、27534
- Wayne Memorial Hospital
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Winston-Salem、North Carolina、アメリカ、27157
- Wake Forest University Health Sciences
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Ohio
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Columbus、Ohio、アメリカ、43210
- Ohio State University Comprehensive Cancer Center
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73104
- University of Oklahoma Health Sciences Center
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15224
- West Penn Hospital
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Rhode Island
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Providence、Rhode Island、アメリカ、02903
- Rhode Island Hospital
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Providence、Rhode Island、アメリカ、02906
- Miriam Hospital
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Vermont
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Berlin、Vermont、アメリカ、05602
- Central Vermont Medical Center/National Life Cancer Treatment
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Burlington、Vermont、アメリカ、05405
- University of Vermont College of Medicine
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
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：なし
- 介入モデル：単一グループの割り当て
- 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 |
|---|---|
|
実験的：Treatment (chemotherapy, PBSC or bone marrow transplantation)
See Detailed Description.
|
相関研究
与えられた IV
他の名前：
与えられた IV
他の名前：
相関研究
与えられた IV
他の名前：
与えられた IV
他の名前：
与えられた SC
他の名前：
与えられた IV
他の名前：
Undergo autologous bone marrow transplantation
他の名前：
Undergo autologous PBSC transplantation
他の名前：
|
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 |
|---|---|---|
|
Number of Participants Who Completed Maintenance Decitabine.
時間枠：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
|
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Disease-free Survival (DFS) Rate at 1 Year
時間枠：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
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Relationship Between Busulfan Pharmacokinetics (Area Under the Curve) and Relapsed Disease
時間枠：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.
|
At baseline, after 2, 4, and 6 hours after the start of busulfan infusion
|
協力者と研究者
捜査官
- 主任研究者：William Blum、Alliance for Clinical Trials in Oncology
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
- 組織型別の新生物
- 新生物
- 白血病
- 白血病、骨髄性
- 白血病、骨髄性、急性
- 薬の生理作用
- 薬理作用の分子機構
- 抗感染剤
- 抗ウイルス剤
- 酵素阻害剤
- 代謝拮抗薬、抗腫瘍薬
- 代謝拮抗剤
- 抗悪性腫瘍薬
- 免疫抑制剤
- 免疫学的要因
- チューブリンモジュレーター
- 抗有糸分裂剤
- 有糸分裂モジュレーター
- 抗悪性腫瘍薬、アルキル化
- アルキル化剤
- 骨髄破壊的アゴニスト
- 抗悪性腫瘍剤、ファイトジェニック
- トポイソメラーゼ II 阻害剤
- トポイソメラーゼ阻害剤
- 皮膚科用薬
- アジュバント、免疫
- 抗生物質、抗悪性腫瘍薬
- 角質溶解剤
- エトポシド
- エトポシドリン酸塩
- デシタビン
- ポドフィロトキシン
- レノグラスチム
- シタラビン
- ダウノルビシン
- ブスルファン
その他の研究ID番号
- NCI-2009-00444 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- U10CA180821 (米国 NIH グラント/契約)
- U10CA031946 (米国 NIH グラント/契約)
- CDR0000521603
- CALGB 10503 (その他の識別子：Alliance for Clinical Trials in Oncology)
- CALGB-10503 (その他の識別子：CTEP)
- R21CA128377 (米国 NIH グラント/契約)
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。