A PHASE III STUDY IN CHILDREN WITH UNTREATED ACUTE MYELOGENOUS LEUKEMIA (AML) OR MYELODYSPLASTIC SYNDROME (MDS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 880
- 试验地点
- 1
- 主要终点
- Proportions of patients achieving remission rate during induction therapy
研究概览
简要总结
Randomized phase III trial to compare the effectiveness of different chemotherapy regimens with or without bone marrow transplantation in treating children who have acute myelogenous leukemia or myelodysplastic syndrome. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia or myelodysplastic syndrome
详细描述
OBJECTIVES:
Increase the remission induction rate to greater than 85% in children with untreated acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) by replacing daunorubicin (DNR) with idarubicin (IDA) in intensively timed DCTER chemotherapy (dexamethasone, cytarabine (ARA-C), thioguanine, etoposide, and daunorubicin) in the first 4 days of each course.
Increase the remission rate further by comparing the efficacy of consolidation chemotherapy with intensively timed IDA DCTER/DCTER vs fludarabine (FAMP), ARA-C, and IDA in maintaining remission and in achieving remission in patients with M2 disease (5%-29% blasts in marrow) at the end of induction chemotherapy.
Compare overall survival, event-free survival, and disease-free survival in patients who receive consolidation with IDA DCTER/DCTER vs FAMP, ARA-C, and IDA.
Compare overall survival, event-free survival, and disease-free survival in patients receiving intensification with the Capizzi II regimen (high-dose ARA-C and asparaginase) vs those receiving a matched-related allogeneic bone marrow transplantation.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed previously untreated acute myeloid leukemia (AML) in patients 1 month to 21 years of age
- •Infants under 1 month with progressive disease eligible
- •Supportive care may be given to confirm that the leukemia is not regressing prior to entry
- •No acute promyelocytic leukemia (FAB M3)
- •No acute undifferentiated leukemia (FAB M0)
- •Histochemical verification of AML required by the following stains:
- •Wright or Giemsa
- •Peroxidase
- •Chloroacetate esterase
- •Sudan black
- •Nonspecific esterase (NSE) with and without fluoride (NaF) inhibition
- •Combined NSE/NaF and butyrate inhibition or diagnosis of megakaryoblasticleukemia (FAB M7) should be supported by one of the following:
- •CD41 reactivity
- •Glycoprotein 1b reactivity
- •Factor VIII-related antigen reactivity
- •Platelet peroxidase on electron microscopy
- •The following are also eligible:
- •Myelodysplastic syndromes, including:
- •Refractory anemia (RA) *
- •RA with ringed sideroblasts (RARS) *
- •RA with excess blasts (RAEB)
- •RAEB in transformation (RAEBt)
- •Chronic myelomonocytic leukemia (CMML)
- •AML with monosomy 7
- •Granulocytic sarcoma (chloroma) with or without marrow involvement
- •Mixed lineage leukemia with 2 morphologically defined populations provided the predominant population is myeloid
- •No Downs syndrome
- •No juvenile chronic myelogenous leukemia
- •No Fanconi's anemia
- •No secondary AML
- •Performance status - Not specified
- •No prior anticancer chemotherapy
- •Prior topical or inhaled steroids for nonmalignant conditions allowed
- •No prior anticancer radiotherapy
- •No prior antileukemic therapy
排除标准
- 未提供
研究组 & 干预措施
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: daunorubicin hydrochloride (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: therapeutic hydrocortisone (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: allogeneic bone marrow transplantation (Procedure)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: filgrastim (Biological)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: cytarabine (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: idarubicin (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: dexamethasone (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: thioguanine (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: etoposide (Drug)
Arm I (combination chemotherapy)
Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10.
See Detailed Description
干预措施: methotrexate (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: asparaginase (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: fludarabine phosphate (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: therapeutic hydrocortisone (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: allogeneic bone marrow transplantation (Procedure)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: filgrastim (Biological)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: cytarabine (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: idarubicin (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: thioguanine (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: methotrexate (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: cyclophosphamide (Drug)
Arm II (combination chemotherapy)
Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study.
Intensification: See Detailed Description
干预措施: busulfan (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: daunorubicin hydrochloride (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: filgrastim (Biological)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: cytarabine (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: idarubicin (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: dexamethasone (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: thioguanine (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: etoposide (Drug)
Arm III (combination chemotherapy, aldesleukin)
Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.
干预措施: aldesleukin (Biological)
Arm IV (combination chemotherapy)
No further treatment
干预措施: daunorubicin hydrochloride (Drug)
Arm IV (combination chemotherapy)
No further treatment
干预措施: filgrastim (Biological)
Arm IV (combination chemotherapy)
No further treatment
干预措施: cytarabine (Drug)
Arm IV (combination chemotherapy)
No further treatment
干预措施: idarubicin (Drug)
Arm IV (combination chemotherapy)
No further treatment
干预措施: dexamethasone (Drug)
Arm IV (combination chemotherapy)
No further treatment
干预措施: thioguanine (Drug)
Arm IV (combination chemotherapy)
No further treatment
干预措施: etoposide (Drug)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: daunorubicin hydrochloride (Drug)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: 3-dimensional conformal radiation therapy (Radiation)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: filgrastim (Biological)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: cytarabine (Drug)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: idarubicin (Drug)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: dexamethasone (Drug)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: thioguanine (Drug)
Arm V (combination chemotherapy, radiotherapy)
Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.
干预措施: etoposide (Drug)
结局指标
主要结局
Proportions of patients achieving remission rate during induction therapy
时间窗: Up to 42 days
Proportion of patients dying or with residual disease during induction therapy
时间窗: Up to 42 days
Time to marrow recovery (induction phase)
时间窗: Up to 42 days
Frequency of toxicities, including infectious complications (induction phase)
时间窗: Up to 42 days
Marrow status
时间窗: At 14 days
Percent of blasts
时间窗: At the end of induction therapy
Complete remission at the end of consolidation therapy
时间窗: Up to 5 years
Survival following consolidation
时间窗: Up to 5 years
Event-free survival following consolidation
时间窗: Up to 5 years
Overall survival (intensification)
时间窗: Up to 5 years
EFS (intensification)
时间窗: Up to 5 years
次要结局
未报告次要终点