Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) Autologous Stem Cell Support for Resistant or Recurrent High-Risk Neuroblastoma (IND 69-112)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 9
- 主要终点
- To determine the maximum tolerated dose(MTD) and the toxicities of Melphalan (L-PAM) escalated in the presence of Buthionine sulphoxamine (BSO) and followed by autologous stem cells rescue for pediatric patients with high-risk neuroblastoma.
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 chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of melphalan and buthionine sulfoximine followed by bone marrow or peripheral stem cell transplantation in treating children who have resistant or recurrent neuroblastoma.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of melphalan when combined with buthionine sulfoximine and followed by autologous bone marrow or peripheral blood stem cell support in children with resistant or recurrent high-risk neuroblastoma.
- Assess the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the response rate of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of melphalan.
Patients receive buthionine sulfoximine IV as a bolus over 30 minutes followed by a 72-hour continuous infusion beginning on day -4; melphalan IV over 15 minutes on days -3 and -2; autologous peripheral blood stem cells or bone marrow IV over 15-30 minutes on day 0; and filgrastim (G-CSF) subcutaneously or IV once daily beginning on day 0 and continuing until blood counts recover.
Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
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 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients have relapsed neuroblastoma and must have exhausted all other options for treatment before they can be considered for treatment on this study.
- •Relapsed patients who are greater than 6 months since having a stem cell transplant can enter on this study.
- •Patients must have stem cells collected and stored before starting treatment.
- •Patients must have a double lumen central venous line in place.
- •Patients must have adequate kidney and liver function measured by blood tests and test of renal function (creatinine clearance or glomerular filtration rate (GFR)).
- •Patients must have normal heart and lung function measured by lack of physical evidence or clinical history of difficulties breathing and tests of cardiac function (Echocardiogram or MUGA evaluation).
- •Patients must have an essentially normal neurological exam.
- •Patients must have one entire kidney that has not had any radiation at treatment doses. (Xrays and scans are ok).
- •Patients must have recovered from the effects of any prior treatment for their tumor.
排除标准
- •They have had any radiation therapy to the brain.
- •They have known history of or current tumor found in the brain or surrounding tissues.
- •They have a history of seizures.
- •They have a history of changes in a test of kidney function with antibiotic use in the 6 months immediately before entering on this study.
研究组 & 干预措施
Single Group
干预措施: buthionine sulfoximine (Drug)
Single Group
干预措施: melphalan (Drug)
Single Group
干预措施: Peripheral blood stem cell infusion (Procedure)
Single Group
干预措施: Filgrastim (Other)
结局指标
主要结局
To determine the maximum tolerated dose(MTD) and the toxicities of Melphalan (L-PAM) escalated in the presence of Buthionine sulphoxamine (BSO) and followed by autologous stem cells rescue for pediatric patients with high-risk neuroblastoma.
时间窗: Within 4 weeks of completion of BSO/L-PAM therapy
次要结局
- To determine the glutathione content of peripheral blood leucocytes in patients receiving BSO and L-PAM.(For BSO: just before start of therapy to 8 hours post end of 72 infusion. For L-PAM : just before start of 2nd dose to 4 hours post.)
- To determine the pharmacokinetics (PK) of BSO and L-PAM in pediatric patients.(For BSO: just before start of therapy to 8 hours post end of 72 infusion. For L-PAM : just before start of 2nd dose to 4 hours post.)
- To determine the response rate of recurrent high risk neuroblastoma to BSO/LPAM within the confines of a phase I study.(84 days after completion of therapy with BSO/L-PAM and Stem cell re-infusion.)
- To determine the number of days to ANC =/> 500 for three days and platelets =/> 20,000 for three days (without transfusion) for this regimen.(Maximum 56 days after completion of therapy with BSO/L-PAM and Stem cell re-infusion.)