A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 59
- 主要终点
- Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein
研究概览
简要总结
RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other GD2-positive tumors.
- Determine the toxicity and pharmacokinetics of the fusion protein in these patients.
- Determine the effect of the fusion protein on systemic immune modulation in these patients.
- Quantitate the antifusion protein antibodies in patients treated with fusion protein.
- Evaluate antitumor responses resulting from this fusion protein regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive hu14.18-interleukin-2 (hu14.18-IL2) fusion protein IV over 4 hours once daily on days 1-3. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of hu14.18-IL2 fusion protein until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed neuroblastoma or melanoma at original diagnosis
- •Refractory to chemotherapy or recurrence after prior multiagent chemotherapy
- •Measurable or evaluable (detectable by bone scan) metastatic disease OR
- •No evidence of disease if complete response to prior surgical resection, radiotherapy, and/or chemotherapy OR
- •Histologically confirmed tumor expressing GD2 antigen at original diagnosis or relapse
- •Refractory to standard treatment
- •Measurable or evaluable disease by clinical assessments or laboratory markers OR
- •No evidence of disease after prior surgical resection of metastatic, recurrent disease
- •Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy allowed
- •Soft tissue sarcoma allowed
- •No primary CNS tumors
- •Prior CNS metastases allowed, provided:
- •Disease previously treated
- •Disease clinically stable for 4 weeks before study
- •At least 4 weeks since prior steroids for CNS metastases
- •No clinically detectable pleural effusions or ascites
- •PATIENT CHARACTERISTICS:
- •21 and under
- •Performance status:
- •Karnofsky 60-100% for children over age 10
- •Lansky 60-100% for children age 10 and under
- •Life expectancy:
- •At least 12 weeks
- •Hematopoietic:
- •Absolute neutrophil count greater than 1,000/mm^3
- •Platelet count at least 75,000/mm^3 (transfusion allowed)
- •Hemoglobin at least 9.0 g/dL (transfusion allowed)
- •Bilirubin less than 1.5 mg/dL
- •ALT or AST no greater than 2.5 times normal
- •Hepatitis B surface antigen negative
- •Creatinine no greater than 1.5 mg/dL OR
- •Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min
- •Cardiovascular:
- •Shortening fraction at least 27% by echocardiogram OR
- •Ejection fraction more than 50% by MUGA scan
- •No congestive heart failure
- •No uncontrolled cardiac rhythm disturbance
- •FEV_1 and FVC more than 60% of predicted OR
- •No dyspnea at rest
- •No exercise intolerance
- •Oxygen saturation more than 94% by pulse oximetry on room air
- •Neurologic:
- •No seizure disorders requiring antiseizure medications
- •No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •No significant concurrent illnesses unrelated to cancer or its treatment
- 另有 33 项未显示
排除标准
- 未提供
研究组 & 干预措施
DG2 positive relapsed or refractory solid tumors
The initial hu14.18-IL2 fusion protein (FP) dose will be 2 mg/m2 given intravenously over 4 hours, daily for 3 days. Five separate dose levels are scheduled: 2 mg/m²/dose (IV over 4 hours) x 3 days, 4 mg/m²/dose (IV over 4 hours) x 3 days, 6 mg/m²/dose (IV over 4 hours) x 3 days, 8 mg/m²/dose (IV over 4 hours) x 3 days, 10 mg/m²/dose (IV over 4 hours) x 3 days.
干预措施: hu14.18-IL2 fusion protein (Biological)
结局指标
主要结局
Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein
Determine the MTD of hu14.18-IL2 fusion protein and determine the pharmacokinetics of the fusion protein when given as I.V. injections
次要结局
- Assess immunological changes associated with fusion protein therapy