A Children's Oncology Group Pilot Study for the Treatment of Very High Risk Acute Lymphoblastic Leukemia in Children and Adolescents (Imatinib (STI571, GLEEVEC) NSC#716051)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Feasibility, in terms of patient accrual
研究概览
简要总结
This phase II trial is studying how well combination chemotherapy with or without donor peripheral stem cell transplant works in treating children with acute lymphoblastic leukemia. Giving combination chemotherapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
详细描述
PRIMARY OBJECTIVES:
I. Determine the feasibility of treatment with intensified chemotherapy, in terms of toxicity and patient accrual, in children with very high-risk acute lymphoblastic leukemia.
II. Determine the feasibility and efficacy of following intensified chemotherapy with allogeneic hematopoietic stem cell transplantation in patients with HLA-matched related donors.
III. Determine the toxicity of imatinib mesylate in combination with intensified chemotherapy in Philadelphia chromosome-positive patients.
IV. Determine the event-free survival of patients treated with this regimen. V. Determine whether minimal residual disease (MDR) after induction therapy and prior to intensification therapy can predict relapse 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
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of acute lymphoblastic leukemia
- •Received prior front-line therapy on a Pediatric Oncology Group (POG),Children's Cancer Group (CCG), or Central Oncology Group (COG) study
- •Received induction therapy comprising vincristine, asparaginase, prednisone/dexamethasone, and daunorubicin as in CCG, POG, or COG protocols
- •M1 or M2 bone marrow status after front-line induction therapy and presenting with at least 1of the following:
- •Philadelphia chromosome positive (Ph+) with t(9;22)(q34;q11) by cytogenetics or fluorescence in situ hybridization
- •bcr-abl fusion transcript by reverse transcription polymerase chain reaction
- •Hypodiploid with less than 44 chromosomes and/or DNA index less than0.81
- •MLL translocation (11q23) by cytogenetics and a slow early response (SER) to induction therapy, defined as at least 5% blasts at day 15 of induction and/or at least .1% minimal residual disease (MRD) after induction therapy
- •Failed to achieve remission after front-line induction therapy
- •M3 bone marrow status (greater than 25% blasts) after induction therapy
- •M2 bone marrow status (5-25% blasts) or at least 1% MRD after induction therapy and M2 or M3or at least 1% MRD after consolidation therapy (CCG studies) or extended induction therapy (POG or COG studies)
- •See Disease Characteristics
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •See Disease Characteristics
- •See Disease Characteristics
- •No concurrent prophylactic cranial radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Arm I
See Design Details.
干预措施: vincristine sulfate (Drug)
Arm I
See Design Details.
干预措施: filgrastim (Biological)
Arm I
See Design Details.
干预措施: asparaginase (Drug)
Arm I
See Design Details.
干预措施: cyclophosphamide (Drug)
Arm I
See Design Details.
干预措施: cyclosporine (Drug)
Arm I
See Design Details.
干预措施: cytarabine (Drug)
Arm I
See Design Details.
干预措施: daunorubicin hydrochloride (Drug)
Arm I
See Design Details.
干预措施: dexamethasone (Drug)
Arm I
See Design Details.
干预措施: etoposide (Drug)
Arm I
See Design Details.
干预措施: ifosfamide (Drug)
Arm I
See Design Details.
干预措施: imatinib mesylate (Drug)
Arm I
See Design Details.
干预措施: leucovorin calcium (Drug)
Arm I
See Design Details.
干预措施: mercaptopurine tablet (Drug)
Arm I
See Design Details.
干预措施: methotrexate (Drug)
Arm I
See Design Details.
干预措施: pegaspargase (Drug)
Arm I
See Design Details.
干预措施: allogeneic bone marrow transplantation (Procedure)
Arm I
See Design Details.
干预措施: peripheral blood stem cell transplantation (Procedure)
Arm I
See Design Details.
干预措施: umbilical cord blood transplantation (Procedure)
Arm I
See Design Details.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Feasibility, in terms of patient accrual
时间窗: Up to 1.75 years
As a target goal, we wish to enroll at least 80% of the potential available patients. The accrual duration for this pilot study will be based on accruing adequate numbers to complete the dose escalation study in the Ph+ subset. The planned study accrual duration should be approximately 1.75 years.
Feasibility, in terms of incidence of adverse events graded according to NCI CTC v 2.0
时间窗: Up to 7 years
The use of imatinib as given in combination with other agents in a particular cohort will be considered feasible initially if 5 or more of the first 6 evaluable patients complete the phase(s) without evidence of grade 3 or 4 targeted toxicities.
次要结局
- Event-free survival(Up to 7 years)