Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP
试验速览
- 阶段
- 2 期
- 入组人数
- 279
- 试验地点
- 83
- 主要终点
- Proportion of patients able to start continuation therapy (Phase II)
研究概览
简要总结
RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether gemtuzumab ozogamicin is more effective than standard supportive care in treating older patients who have acute myeloid leukemia.
PURPOSE: This randomized phase II/III trial is studying two different gemtuzumab ozogamicin regimens to see how well they work compared to standard supportive care in treating older patients with previously untreated acute myeloid leukemia.
详细描述
OBJECTIVES:
- Compare the feasibility, toxicity, and antileukemic activity of two different dosing regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients with previously untreated acute myeloid leukemia who are not candidates for intensive chemotherapy. (phase II)
- Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase II vs standard supportive care, in terms of overall survival, in these patients. (phase III)
OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over), CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status (0-1 vs 2 vs 3-4), and participating center.
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Phase II: Patients are randomized to 1 of 3 treatment arms.
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Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and 8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
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Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
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Arm III: Patients receive standard supportive care.
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Phase III: Patients are randomized to 1 of 2 treatment arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 61 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed acute myeloid leukemia (AML)
- •At least 20% bone marrow blasts by bone marrow aspiration or biopsy
- •All subtypes except M3 (acute promyelocytic leukemia) are allowed
- •Previously untreated primary or secondary disease (including AML after myelodysplastic syndromes)
- •Ineligible for intensive chemotherapy, as defined by 1 of the following criteria:
- •61 to 75 years old AND WHO performance status > 2 AND/OR unwilling to receive intensive chemotherapy
- •Over 75 years old
- •No blast crisis of chronic myeloid leukemia
- •No AML supervention after other myeloproliferative disease
- •WBC < 30,000/mm^3 and meets 1 of the following criteria:
- •WBC < 30,000/mm^3 at diagnosis AND had no prior treatment with hydroxyurea
- •WBC ≥ 30,000/mm^3 at diagnosis AND received mandatory pretreatment with hydroxyurea (up to 14 days duration) until WBC < 30,000/mm^3
- •No active CNS leukemia
- •PATIENT CHARACTERISTICS:
- •See Disease Characteristics
- •61 and over
- •Performance status
- •See Disease Characteristics
- •Life expectancy
- •Not specified
- •Hematopoietic
- •See Disease Characteristics
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •Creatinine ≤ 1.5 times ULN
- •Cardiovascular
- •No arrhythmia requiring chronic treatment
- •No congestive heart failure
- •No symptomatic ischemic heart disease
- •No other severe cardiovascular disease
- •No severe pulmonary dysfunction ≥ grade 3
- •No alcohol abuse
- •No severe neurological or psychiatric disease
- •No active uncontrolled infection or severe systemic infection
- •No other malignancy
- •No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
- •HIV negative
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
- •No concurrent antiangiogenic drugs
- •Chemotherapy
- •See Disease Characteristics
- •Concurrent low-dose cytostatic agents (i.e., thioguanine or mercaptopurine) allowed for palliative care (standard supportive care arm only)
- •Endocrine therapy
- •Prior corticosteroids (duration ≤ 14 days ) for primary or secondary AML allowed
- •Radiotherapy
- •Not specified
- •Not specified
- •No other concurrent cytotoxic drugs
- 另有 2 项未显示
排除标准
- 未提供
结局指标
主要结局
Proportion of patients able to start continuation therapy (Phase II)
Overall survival (Phase III)
次要结局
- Rate of complete remission (CR+CRp)by the end of continuation therapy, for patients in the GO arms (Phase II)
- Overall survival (Phase II)
- Toxicity (CTCAE grading), including time to hematological recovery (Phase II & III)
- Rate of complete remisison (CR+CRp) by the end of induction and by the end of continuation therapy, for patients in GO arm (Phase III)
- Disease-free survival for patients who reached CR or CRp (Phase III)
- Progression-free survival from randomization for patients in GO arm (Phase III)