Cytarabine and Daunorubicin With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Randomised Induction and Post Induction Therapy in Older Patients (≥61 Years of Age) With Acute Myeloid Leukemia (AML) and Refractory Anemia With Excess Blasts (RAEB, RAEB-t)
RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether cytarabine and daunorubicin followed by gemtuzumab ozogamicin is more effective than cytarabine and daunorubicin in treating acute myeloid leukemia or myelodysplastic syndromes.
PURPOSE: This randomized phase III trial is studying cytarabine and two different doses of daunorubicin to see how well they work compared to cytarabine and daunorubicin followed by gemtuzumab ozogamicin in treating older patients with acute myeloid leukemia or myelodysplastic syndromes.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Compare the event-free and disease-free survival of older patients with acute myeloid leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation treated with induction therapy comprising cytarabine in combination with two different doses of daunorubicin followed by cytarabine alone with or without post-induction therapy comprising gemtuzumab ozogamicin.
Secondary
- Compare the complete remission rate in patients treated with these regimens.
- Compare the overall survival of patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Determine the probability of relapse and death during first complete remission in patients treated with post-induction gemtuzumab ozogamicin.
- Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or cytogenetics) with probability of complete remission and overall, event-free, and disease-free survival of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic syndromes [MDS]) for induction therapy. Patients are stratified according to participating center, diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction therapy (complete remission [CR] vs no CR) for post-induction therapy.
Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment arms.
- Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 3 hours on days 1-3.
- Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but at a higher dose.
Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows evidence of resistant disease), patients in both arms proceed to course 2 of induction therapy.
- Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice daily on days 1-6.
After completion of course 2, patients undergo assessment of remission status. Patients who do not achieve CR are removed from the study. Patients achieving CR proceed to post-induction therapy and undergo a second randomization.
Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment arms.
- Arm I: Patients receive no further chemotherapy.
- Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and 57 in the absence of disease relapse or unacceptable toxicity.
After completion of study treatment, patients are followed monthly for 1 year, every 3 months for 2 years, every 4-6 months for 2 years, and then periodically thereafter.
PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.
研究の種類
入学 (予想される)
段階
- フェーズ 3
連絡先と場所
研究場所
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England
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Basingstoke、England、イギリス、RG24 9NA
- North Hampshire Hospital
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Canterbury、England、イギリス、CT2 7NR
- Kent and Canterbury Hospital
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Gillingham Kent、England、イギリス、ME7 5NY
- Medway Maritime Hospital
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Maidstone、England、イギリス、ME16 9QQ
- Maidstone Hospital
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Truro, Cornwall、England、イギリス、TR1 3LJ
- Royal Cornwall Hospital
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Wales
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Cardiff、Wales、イギリス、CF14 4XW
- University Hospital of Wales
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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
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed diagnosis of 1 of the following:
Acute myeloid leukemia (AML)
M0-M2 or M4-M7 FAB subtype
- No AML with cytogenetic abnormality t(15;17) (M3)
- Patients with secondary AML progressing from prior myelodysplasia* or biphenotypic leukemia are eligible
Refractory anemia with excess blasts (RAEB) or RAEB in transformation
- International Prognostic Scoring System score ≥ 1.5 NOTE: *Any prior hematological disease of ≥ 4 months duration
- No chronic myelogenous leukemia in blastic crisis
- No prior polycythemia rubra vera
- No primary myelofibrosis
PATIENT CHARACTERISTICS:
Age
- 61 and over
Performance status
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- ALT and/or AST ≤ 2.5 times upper limit of normal (ULN)*
- Bilirubin ≤ 2 times ULN* NOTE: *Unless elevation is caused by organ infiltration by AML
Renal
- Creatinine ≤ 2 times ULN* NOTE: *Unless elevation is caused by organ infiltration by AML
Cardiovascular
- No myocardial infarction within the past 6 months
- LVEF > 50% by MUGA, echocardiogram, or other methods
- No unstable angina
- No unstable cardiac arrhythmia
- No severe and/or uncontrolled hypertension
Other
- No uncontrolled diabetes
- No severe and/or uncontrolled infection
- No other severe and/or uncontrolled medical condition
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 6 months since prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- No prior induction therapy for AML or myelodysplastic syndromes
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：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 |
|---|---|
|
アクティブコンパレータ：Arm A low dose Dauno
Induction 45 mg Dauno
|
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実験的：ARM B high dose Dauno
Induction 90 mg Dauno
|
|
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介入なし：Arm 1 no further treatment
|
|
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実験的：Arm 2 Mylotarg
Post induction treatment with Mylotarg
|
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 |
|---|
|
Event-free survival after induction therapy
|
|
Disease-free survival after maintenance therapy
|
二次結果の測定
結果測定 |
|---|
|
Complete remission (CR) rate after induction therapy
|
|
Overall survival after induction therapy
|
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Toxicity after induction therapy
|
|
Toxicity after maintenance therapy
|
|
Probability of relapse and death in first CR after maintenance therapy
|
|
Overall survival after maintenance therapy
|
協力者と研究者
捜査官
- スタディチェア：Jonathan Kell, MRCPath、University Hospital of Wales
研究記録日
主要日程の研究
研究開始
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 (見積もり)
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
キーワード
- 過剰な芽球を伴う難治性貧血
- 形質転換中の過剰な芽球を伴う難治性貧血
- de novo 骨髄異形成症候群
- 二次性骨髄異形成症候群
- 11q23 (MLL) 異常を伴う成人急性骨髄性白血病
- inv(16)(p13;q22)を伴う成人急性骨髄性白血病
- t(16;16)(p13;q22)を伴う成人急性骨髄性白血病
- t(8;21)(q22;q22)を伴う成人急性骨髄性白血病
- 続発性急性骨髄性白血病
- 未治療の成人急性骨髄性白血病
- 成人急性巨核芽球性白血病 (M7)
- 成人急性低分化型骨髄性白血病 (M0)
- 成人急性単芽球性白血病 (M5a)
- 成人急性単球性白血病 (M5b)
- 成熟を伴う成人急性骨髄芽球性白血病（M2）
- 成熟していない成人急性骨髄芽球性白血病 (M1)
- 成人急性骨髄単球性白血病 (M4)
- 成人赤白血病 (M6a)
- 成人純粋赤血球性白血病 (M6b)
追加の関連 MeSH 用語
その他の研究ID番号
- CDR0000433422
- SAKK-AML-43
- EU-20514
- HOVON-AML-43
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