I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 29
- 主要终点
- Response (Complete Response, Very Good Partial Response, and Partial Response) at 60-days Post Stem Cell Infusion
研究概览
简要总结
RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more tumor cells are killed. Giving radiation therapy after an autologous peripheral stem cell or bone marrow transplant may kill any remaining tumor cells.
PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine together with combination chemotherapy and radiation therapy works in treating patients who are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or refractory neuroblastoma.
详细描述
OBJECTIVES:
Primary
- Determine the response rate in patients with relapsed or refractory neuroblastoma treated with iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and combination chemotherapy comprising carboplatin, etoposide, and melphalan followed by autologous bone marrow or peripheral blood stem cell transplantation and radiotherapy.
Secondary
- Determine the hematopoietic and nonhematopoietic toxicity of this regimen in these patients.
- Determine the tumor self-absorbed radiation dose (TSARD) in patients with measurable soft tissue lesions treated with this regimen.
- Correlate the TSARD with tumor response in patients with measurable residual soft tissue disease treated with this regimen.
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 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of relapsed or refractory neuroblastoma
- •Histologically confirmed and/or demonstration of tumor cells in bone marrow with elevated urinary catecholamine metabolites
- •High-risk neuroblastoma must meet one of the following:
- •Progressive disease prior to or after completion of induction therapy
- •Mixed response or no response after completion of 4 courses of induction therapy
- •Partial response after 4 courses of induction therapy allowed provided no prior participation in COG-A3973 or other phase III COG trials
- •Measurable disease, defined as at least one metaiodobenzylguanidine (MIBG)-avid target lesion determined by diagnostic MIBG scan within 6 weeks of study entry (tumor sites that have received local irradiation within 3 months of study entry are not considered target lesions)
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Lansky 60-100% OR
- •Karnofsky 60-100%
- •Life expectancy
- •At least 2 months
- •Hematopoietic
- •Hemoglobin ≥ 10 g/dL
- •Absolute neutrophil count ≥ 750/mm^3
- •Platelet count ≥ 50,000/mm^3 (if no marrow involvement by morphologic exam/no transfusion allowed) (> 20,000/mm^3 if metastatic tumor involvement of marrow by morphologic exam/transfusion allowed)
- •Bilirubin < 1.3 mg/dL
- •SGOT and SGPT < 5 times normal
- •Hepatitis B surface antigen negative
- •Hepatitis C negative
- •Glomerular filtration rate or creatinine clearance ≥ 60 ml/min
- •Creatinine ≤ 1.5 times normal for age as follows:
- •0.8 mg/dL (for patients ≤ 5 years of age)
- •1.0 mg/dL (for patients 6 to 10 years of age)
- •1.2 mg/dL (for patients 11 to 15 years of age)
- •1.5 mg/dL (for patients > 15 years of age)
- •Cardiovascular
- •Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR
- •Fractional shortening ≥ 27% by echocardiogram
- •Normal lung function defined as no dyspnea at rest and no oxygen requirement OR measured oxygen saturation > 93% on room air
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No disease of any major organ system that would preclude study compliance
- •No concurrent hemodialysis
- •No active infection requiring IV antivirals, antibiotics, or antifungals (patients on antifungal therapy are eligible provided they are culture- and biopsy-negative in suspected residual radiographic lesions)
- •Patient weight within limits to receive ≤ maximum total allowable dose of ^131I-MIBG
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •No prior myeloablative transplantation
- •Prior submyeloablative transplantation allowed at discretion of principal investigator
- •More than 3 weeks since prior biologic therapy
- •Chemotherapy
- •More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for mitomycin C or nitrosoureas)
- •No prior melphalan therapy with a total dose of > 100 mg/m^2
- •Radiotherapy
- •See Disease Characteristics
- •At least 6 weeks since prior radiotherapy (6 months for craniospinal or whole lung radiotherapy)
- 另有 8 项未显示
排除标准
- 未提供
研究组 & 干预措施
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: Filgrastim (Biological)
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: 131I-MIBG (Radiation)
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: Peripheral blood stem cell infusion (Procedure)
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: Radiation therapy (Radiation)
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: Carboplatin (Drug)
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: Etoposide (Drug)
All the patients enrolled in the study
This is a single arm study. The following description applies to all the patients who are enrolled in the study:
On Day -21, patients receive 131I-MIBG infusion.
On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan.
On Day -4, patients receive Carboplatin, Etoposide.
On Day -3, Day -2, Day -1, patients rest.
On Day 0, patients receive peripheral blood stem cell infusion.
Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates.
Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0.
Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.
干预措施: Melphalan (Drug)
结局指标
主要结局
Response (Complete Response, Very Good Partial Response, and Partial Response) at 60-days Post Stem Cell Infusion
时间窗: Response assessed 60 days post stem cell infusion
Tumor response based on evaluation performed on day 60 or at the time of disease progression/recurrence or start of another treatment - whichever comes first. Such evaluations will include 123I-MIBG scan, CT/MRI, urine catecholamine measurement, and bone marrow analysis (for those with marrow disease at study entry).
次要结局
- Dose Limiting Veno-occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome SOS(Between start of MIBG treatment and 60 days post stem cell infusion)
- Event-free Survival (EFS) at 3 Years(3 years since start of treatment)
- Engraftment DLT(From treatment start until 60 days post stem cell infusion)
研究者
Nant Operations Center
NANT Operations Center
Children's Hospital Los Angeles