Treatment of Children With Down Syndrome (DS) and Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Transient Myeloproliferative Disorder (TMD): A Phase III Group-Wide Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 254
- 试验地点
- 236
- 主要终点
- Event Free Survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating children who have Down syndrome and myeloproliferative disorder, acute myelogenous leukemia, or myelodysplastic syndrome.
详细描述
OBJECTIVES:
- Evaluate the efficacy of reduced-dose induction and intensification chemotherapy, in terms of remission rate, disease-free survival rate, and acute morbidity and mortality, in children with Down syndrome and acute myelogenous leukemia or myelodysplastic syndromes.
- Define the understanding of the natural history of transient myeloproliferative disorder (TMD) in children with Down syndrome.
- Determine whether there is a reduction of sequelae in long-term survivors after treatment with this regimen.
- Determine the incidence of subsequent leukemia in patients with transient myeloproliferative disorder treated with this regimen.
- Determine the predictive risk factors for developing subsequent leukemia in patients with transient myeloproliferative disorder treated with this regimen.
OUTLINE: This is a multicenter study.
- Group I: Patients are observed if their transient myeloproliferative disorder (TMD) does not require intervention. Patients who require therapy for TMD undergo leukapheresis or exchange transfusion for up to 3 consecutive days. If the TMD does not resolve or there is significant organ involvement, patients receive low-dose cytarabine IV continuously on days 0-4. Treatment repeats at least every 2 weeks for up to 4 courses. Patients who experience a recurrence of TMD at least 8 weeks after resolution or have refractory disease may proceed to group II for further treatment.
- Group II (closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10.
Patients who achieve remission after induction therapy receive 2 courses of intensification therapy, for approximately 4 months. During the first course, patients receive cytarabine IV over 3 hours twice daily on days 0, 1, 7, and 8. Patients also receive asparaginase intramuscularly on days 1 and 8. The second course of therapy comprises CNS prophylaxis. Patients with no CNS disease at diagnosis or whose CNS disease resolved by day 7 of induction therapy receive cytarabine IT on days 0, 7, and 14. Patients with persistent CNS disease on day 7 of induction therapy receive cytarabine IT, hydrocortisone IT, and methotrexate IT on days 0, 7, and 14.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A: TMD patients only
Patients are observed if their transient myeloproliferative disorder (TMD) does not require intervention. Patients who require therapy for TMD undergo leukapheresis or exchange transfusion for up to 3 consecutive days. If the TMD does not resolve or there is significant organ involvement, patients receive low-dose cytarabine IV continuously on days 0-4. Treatment repeats at least every 2 weeks for up to 4 courses. Patients who experience a recurrence of TMD at least 8 weeks after resolution or have refractory disease may proceed to group II for further treatment. patients will continue to be followed for remission induction, EFS, DFS and OS regardless of the type of leukemia that develops.
干预措施: cytarabine (Drug)
Arm B: AML/MDS patients only
(closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
干预措施: asparaginase (Drug)
Arm B: AML/MDS patients only
(closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
干预措施: cytarabine (Drug)
Arm B: AML/MDS patients only
(closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
干预措施: daunorubicin hydrochloride (Drug)
Arm B: AML/MDS patients only
(closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
干预措施: methotrexate (Drug)
Arm B: AML/MDS patients only
(closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
干预措施: therapeutic hydrocortisone (Drug)
Arm B: AML/MDS patients only
(closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
干预措施: thioguanine (Drug)
结局指标
主要结局
Event Free Survival
时间窗: Length of study
次要结局
未报告次要终点