131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Refractory Neuroblastoma and Pheochromocytoma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of patients who receive 131 I-MIBG.
研究概览
简要总结
This is a best available therapy/compassionate use single institution study designed to determine the palliative benefit and toxicity of 131I-MIBG in patients with progressive neuroblastoma and metastatic pheochromocytoma who are not eligible for therapies of higher priority. Patients may receive a range of doses depending on stem cell availability and tumor involvement of bone marrow. Response rate, toxicity, and time to progression and death will be evaluated.
详细描述
Primary Objective is to provide access to therapy with 131I-MIBG for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.
Secondary Objective is to assess disease response to 131I-MIBG therapy for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.
Tertiary Objectives are to 1) gain more information about the toxicities of 131I-MIBG therapy; 2) assess improvement of symptoms, including pain and fatigue, for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are receiving 131I-MIBG therapy.
- The therapeutic dose of 131I-MIBG will be based on the following:
- Minimum dose of 10 mCi/kg for patients without a stem cell source whose renal function is above the upper limit of normal but still meets eligibility criteria.
- Dose of 12 mCi/kg for patients without a stem cell source with normal renal function and meets other eligibility criteria.
- Dose of > 12 mCi/kg to 18 mCi/kg maximum at investigator's discretion for patients meeting eligibility criteria with stem cells available.
- A urinary catheter and intravenous fluids will be used for bladder protection, and potassium iodide solution for thyroid Protection.
- G-CSF is recommended for patients with ANC less than 750 after MIBG infusion.
- hematopoietic stem cell infusion is recommended for patients with grade 4 hematologic toxicity following 131I-MIBG therapy that continues to have an ANC <200 on G-CSF without signs of recovery for >2 weeks and any patient requiring platelet transfusion more than two times weekly for 4 consecutive weeks.
- Follow-up will be done until disease progression, death or other therapies are initiated.
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis:
- •Relapsed/refractory neuroblastoma with original diagnosis based on tumor histopathology or elevated urine catecholamines with typical neuroblastoma cells in the bone marrow
- •Metastatic pheochromocytoma
- •Age >1 year and able to cooperate with radiation safety restrictions during therapy period
- •Karnofsky or Lansky performance status of ≥ 50%
- •Life expectancy: ≥ at least 8 weeks
- •Disease status: Failure to respond to standard therapy or development of progressive disease at any time.
- •Disease must be evaluable by MIBG scan. A positive MIBG scan must be present within 8 weeks prior to study entry and subsequent to any intervening therapy. If the patient has only one MIBG positive lesion and that lesion was radiated, a biopsy must be done at least 4 weeks after radiation was completed and must show viable neuroblastoma.
- •Stem Cells: Patients must have a hematopoietic stem cell product available for reinfusion after MIBG treatment at doses of > 12 mCi/kg.
- •Have acceptable organ function as defined below within 7 days of enrollment:
- •Bone Marrow: ANC ≥750 X 109 /L and platelets ≥50,000 X 109 /L without transfusion if stem cells are not available (any ANC or platelet allowed if stem cells available)
- •Renal: Creatinine ≤3x upper limit of normal
- •Hepatic: Bilirubin ≤2x upper limit of normal; AST/ALT ≤10x upper limit of normal
- •Cardiac: Ejection fraction ≥45% on echocardiogram
- •Pulmonary: normal lung function as manifested by no dyspnea and/or oxygen saturation ≥ 88% on room air.
- •Prior Therapy: Patients must have recovered from all acute toxicities (defined as CTCAE 4.0 ≤ grade 1) associated with any prior therapy, and:
- •Myelosuppressive chemotherapy: At least 2 weeks should have elapsed since any chemotherapy causing myelosuppression
- •Biologic (anti-neoplastic agent): At least 7 days should have elapsed since the completion of therapy with a biologic agent.
- •Monoclonal antibodies: At least 3 half-lives should have elapsed since therapy with a monoclonal antibody
- •Radiation therapy: Three-months should have elapsed in the case of completing radiation to any of the following fields: craniospinal, total abdominal, whole lung, total body irradiation). For all other sites of radiation, at least 2 weeks should have relapsed.
- •Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, IL-2): must be discontinued a minimum of 24 hours prior to MIBG therapy.
- •Voluntary written informed consent
排除标准
- •Patients with disease of any major organ system that would compromise their ability to withstand therapy.
- •Because of the teratogenic potential of the study medication, no patients who are pregnant or lactating will be allowed. Patients of childbearing potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus.
- •Known allergy to any of the agents or their ingredients used in this study.
- •Patients who are on hemodialysis
- •Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies
研究组 & 干预措施
131 I-MIBG Treatment Arm
Therapeutic 131 I-Metaiodobenzylguanidine (131I-MIBG) will be infused intravenously, intravenous fluids will be administered to help maintain urine flow and isotope excretion. Potassium iodide solution will be administered to protect thyroid function. G-CSF will be used if necessary for neutrophil recovery. Hematopoietic stem cell infusion if meets the criteria.
干预措施: 131 I-Metaiodobenzylguanidine (131I-MIBG) (Drug)
131 I-MIBG Treatment Arm
Therapeutic 131 I-Metaiodobenzylguanidine (131I-MIBG) will be infused intravenously, intravenous fluids will be administered to help maintain urine flow and isotope excretion. Potassium iodide solution will be administered to protect thyroid function. G-CSF will be used if necessary for neutrophil recovery. Hematopoietic stem cell infusion if meets the criteria.
干预措施: Potassium iodide solution (Drug)
131 I-MIBG Treatment Arm
Therapeutic 131 I-Metaiodobenzylguanidine (131I-MIBG) will be infused intravenously, intravenous fluids will be administered to help maintain urine flow and isotope excretion. Potassium iodide solution will be administered to protect thyroid function. G-CSF will be used if necessary for neutrophil recovery. Hematopoietic stem cell infusion if meets the criteria.
干预措施: G-CSF (Drug)
131 I-MIBG Treatment Arm
Therapeutic 131 I-Metaiodobenzylguanidine (131I-MIBG) will be infused intravenously, intravenous fluids will be administered to help maintain urine flow and isotope excretion. Potassium iodide solution will be administered to protect thyroid function. G-CSF will be used if necessary for neutrophil recovery. Hematopoietic stem cell infusion if meets the criteria.
干预措施: hematopoietic stem cell infusion (Procedure)
结局指标
主要结局
Number of patients who receive 131 I-MIBG.
时间窗: 2 hours
The number of patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who receive access to 131 I-MIBG.
次要结局
- Incidence of hematologic toxicities(1 year)
- Incidence of hepatic toxicities(1 year)
- Improvement of fatigue(56 days)
- Disease response(1 year)
- Incidence of Thyroid Toxicity(1 year)
- Improvement of pain symptoms(56 days)