Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 试验地点
- 30
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different ways may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy.
PURPOSE: This phase I trial is studying the side effects and best dose of combination chemotherapy when given before stem cell transplant and radiation therapy in treating patients with neuroblastoma that has not responded to previous treatments.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose and toxic effects of iodine I 131 metaiodobenzylguanidine (131 I-MIBG) plus ablative doses of carboplatin and etoposide administered with fixed-dose melphalan followed by autologous hematopoietic stem cell transplantation in patients with refractory or residual high-risk neuroblastoma.
- Determine the number of days until blood counts recover in these patients after receiving this treatment regimen.
- Determine the response rate to this treatment regimen in these patients.
- Determine the tumor dosimetry of 131 I-MIBG in patients with measurable soft tissue lesions.
OUTLINE: This is a dose-escalation study of iodine I 131 metaiodobenzylguanidine (131 I-MIBG), carboplatin, and etoposide. Patients are stratified according to glomerular filtration rate (at least 100 mL/min vs 60-99 mL/min).
Patients undergo peripheral blood stem cell harvest or bone marrow harvest at least 2 weeks prior to treatment with 131 I-MIBG.
Patients receive 131 I-MIBG IV over 120 minutes on day -21; melphalan IV on days -7 to -5; carboplatin and etoposide IV continuously over 96 hours on days -7 to -4; autologous hematopoietic stem cell transplantation IV over 15-30 minutes on day 0; and filgrastim (G-CSF) subcutaneously or IV starting on day 0 and continuing until blood counts recover. Radiotherapy is administered to the primary tumor site and metastatic sites twice daily for 7 consecutive days within 6 weeks of transplantation or once blood counts have recovered.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Diagnosis of neuroblastoma as evidenced by one of the following:
- •Histological confirmation
- •Demonstrates clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites
- •High-risk refractory or residual disease
- •Poorly responding disease, meeting 1 of the following criteria:
- •Stable disease or partial response after at least 12 weeks of induction therapy
- •Bone marrow containing greater than 100 tumor cells per 100,000 normal cells after 12 weeks of induction therapy
- •Progressive disease during or after therapy
- •At least 1 prior positive iodine I 131 metaiodobenzylguanidine (131 I-MIBG) scan since diagnosis and meets disease status criteria
- •PATIENT CHARACTERISTICS:
- •1 to 21 (1 to 20 at diagnosis)
- •Performance status:
- •Life expectancy:
- •At least 2 months
- •Hematopoietic:
- •Absolute neutrophil count at least 500/mm^3
- •Platelet count at least 20,000/mm^3 (transfusion allowed)
- •Hemoglobin at least 8 g/dL (transfusion allowed)
- •Bilirubin normal
- •AST/ALT no greater than 3 times normal
- •No active hepatitis (for HIV-positive patients only)
- •Glomerular filtration rate or creatinine clearance at least 60 mL/min
- •Creatinine less than 1.5 times normal for age
- •Cardiovascular:
- •Ejection fraction at least 55% OR
- •Fractional shortening at least 30%
- •No dyspnea at rest or exercise intolerance
- •No requirement for supplemental oxygen
- •No active pneumonia (for HIV-positive patients only)
- •No disease of any major organ system that would preclude study participation
- •No other active health problems (for HIV-positive patients only)
- •No active infections requiring intravenous antivirals, antibiotics, or antifungals
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 3 weeks since prior biologic therapy and recovered
- •Chemotherapy:
- •At least 3 weeks since prior chemotherapy and recovered
- •No more than 100 mg/m^2 total dose of prior melphalan
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •No prior total body, whole abdominal, or whole liver irradiation
- •No prior therapy with 131 I-MIBG
- •At least 2 weeks since prior radiotherapy (6 months for prior radiotherapy to craniospinal or whole lung fields or greater than 50% of bone marrow space) and recovered
- •Prior surgical resection allowed
- •Recovered from prior surgery
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排除标准
- 未提供