The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 205
- 试验地点
- 97
- 主要终点
- Event-free Survival (EFS) at 3 Years
研究概览
简要总结
This phase III trial is studying how well combination chemotherapy works in treating young patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the event-free survival (EFS) and overall survival rates in pediatric patients with Down syndrome (DS) and acute myeloid leukemia AML or myelodysplastic syndromes MDS treated with induction therapy comprising cytarabine, daunorubicin hydrochloride, thioguanine, and asparaginase followed by intensification therapy comprising cytarabine and etoposide.
II. Determine if the EFS rate in these patients can be increased with an intensified course of cytarabine therapy during induction therapy, compared to the EFS rate of patients in protocol COG-A2971.
III. Determine if the number of intrathecal chemotherapy treatments can be reduced in these patients.
IV. Determine if the total cumulative anthracycline dose can be reduced in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 4 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis
- •Diagnosis of myelodysplastic syndromes (MDS) with < 30% blasts or acute myeloid leukemia (AML)
- •Newly diagnosed disease
- •Patients with a history of transient myeloproliferative disorder (TMD) are eligible provided the patient is diagnosed with AML or MDS at > 90 days of age AND meets either of the following criteria:
- •At least 30% blasts in the bone marrow regardless of time since resolution of TMD
- •More than 8 weeks since resolution of TMD with ≥ 5% blasts in the bone marrow
- •Immunophenotype required for study entry
- •No promyelocytic leukemia
- •Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST or ALT < 2.5 times ULN
- •Creatinine adjusted according to age as follows:
- •No greater than 0.4 mg/dL (≤ 5 months)
- •No greater than 0.5 mg/dL (6 months -11 months)
- •No greater than 0.6 mg/dL (1 year-23 months)
- •No greater than 0.8 mg/dL (2 years-5 years)
- •No greater than 1.0 mg/dL (6 years-9 years)
- •No greater than 1.2 mg/dL (10 years-12 years)
- •No greater than 1.4 mg/dL (13 years and over [female])
- •No greater than 1.5 mg/dL (13 years to 15 years [male])
- •No greater than 1.7 mg/dL (16 years and over [male])
- •Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- •No evidence of dyspnea at rest
- •No exercise intolerance
- •Pulse oximetry > 94%
- •No prior chemotherapy, radiotherapy, or any antileukemic therapy
- •Intrathecal cytarabine therapy given at diagnosis allowed
- •Prior therapy for TMD allowed
排除标准
- 未提供
研究组 & 干预措施
Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: asparaginase (Drug)
Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: daunorubicin hydrochloride (Drug)
Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: cytarabine (Drug)
Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: thioguanine (Drug)
Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Event-free Survival (EFS) at 3 Years
时间窗: Time from study entry to induction failure, relapse, or death assessed at 3 years.
Overall Survival (OS) at 3 Years
时间窗: Time from study entry to death, assessed at 3 years.
次要结局
- Induction Remission Rate(End of induction therapy (day 112))
- Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(From the beginning of induction therapy to the end of intensification therapy)
- Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry(At the start of therapy)
- Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis(At baseline and at the end of therapy (intensification) or disease relapse)
- Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry(After Induction I therapy (day 28 from start of therapy))
- Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program(Days 1, 2, 8, and 9 of induction II)
- Gene Expression Profiles by Microarrays(At baseline and at the time of relapse (if available))