A Study of Therapy for Pediatric Relapsed or Refractory Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 2
- 主要终点
- Response Rate
研究概览
简要总结
The main purpose of this study is to find out how well participants with relapsed or refractory ALL respond to treatment with an etoposide- and teniposide-based induction chemotherapy regimen and what the side effects are.
Primary Objectives:
- To estimate the response rate for patients with refractory or relapsed ALL.
- To estimate the survival rate of patients with refractory or relapsed ALL treated with risk-directed therapy.
详细描述
In this study, subjects will be divided into high-risk and standard-risk subgroups according to the length of their first remission, the type of early cancer cell (T or B-cell) and the site or sites of disease relapse. The remission induction phase (the beginning phase of therapy) will consist of three blocks of therapy. Block A features daily IV low-dose etoposide in combination with cytarabine given by continuous IV, weekly vincristine, and daily dexamethasone. In block B, a combination of weekly PEG-asparaginase, vincristine, and daily dexamethasone will be given. Block C will be a combination of high-dose methotrexate, high-dose cytarabine, and teniposide.
There will be two phases of consolidation (treatment phase after induction therapy). Additional therapy will be given between the two consolidation phases. Continuation will consist of eight weekly cycles of chemotherapy. Periodic intrathecal therapy (medicine given into the spinal fluid) will be given throughout the treatment. Participants who do not achieve remission (absence of leukemia) after consolidation will be offered enrollment on St. Jude NKEHM protocol (NK cell transplant). Hematopoietic stem cell transplant (HSCT) is planned for participants with high risk disease. HSCT will be done according to current institutional practice. The duration of chemotherapy will be one year for patients with extramedullary (outside the bone marrow) relapse and two years for all others.
Exploratory objectives include:
- To determine the prevalence of MRD in children undergoing treatment for relapsed ALL and to compare the results to those obtained in children with newly diagnosed ALL.
- To compare the level of MRD in bone marrow and peripheral blood concomitantly in children undergoing treatment for relapsed ALL.
- To characterize the gene expression profile of leukemia cells at the time of diagnosis and relapse to improve our understanding of mechanisms of relapse and of the development of drug resistance.
- To study whether pre-existing or emerging development of serum antibodies to asparaginase is related to hypersensitivity reaction to asparaginase in patient with relapsed ALL.
Detailed Description of Treatment Plan:
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 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
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: Etoposide, cytarabine, vincristine, dexamethasone (Drug)
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: methotrexate, teniposide, PEG-asparaginase (Drug)
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine (Drug)
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: L-asparaginase, erwinia asparaginase (Drug)
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: chemotherapy, intrathecal chemotherapy, steroid therapy (Procedure)
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: Hematopoietic Stem Cell Transplant (Procedure)
Treatment
Participants receive chemotherapy, intrathecal chemotherapy, steroid therapy, hematopoietic stem cell transplant, and natural killer cell transplant as outlined in the Interventions section, including etoposide, cytarabine, vincristine, dexamethasone, methotrexate, teniposide, PEG-asparaginase, mitoxantrone, cyclophosphamide, mercaptopurine, vinblastine, L-asparaginase, erwinia asparaginase.
干预措施: Natural Killer (NK) Cell Transplant (Procedure)
结局指标
主要结局
Response Rate
时间窗: End of re-induction Block C (approximately 1 month after the start of therapy)
The "response rate" is defined as the proportion of participants who attain morphological complete remission after the re-induction Block C, inclusive of all patients who begin re-induction. Morphological complete remission was defined as \<5% blasts in bone marrow by morphology.
Overall Survival (OS)
时间窗: 2 years after last patient completes therapy (approximately 4 years after enrollment)
OS is measured from the start of on-study to the date of death or to the last date of follow-up. Measurement is determined by Kaplan-Meyer estimate. The probability of survival at 5 years after diagnosis is given.
次要结局
未报告次要终点