A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 14
- 主要终点
- Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)
研究概览
简要总结
Phase I trial to compare the effectiveness of interleukin-12 with or without interleukin-2 in treating young patients who have refractory or recurrent neuroblastoma. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining interleukin-2 with interleukin-12 may kill more tumor cells.
详细描述
OBJECTIVES:
I. Define the maximum tolerated dose and dose-limiting toxicity of interleukin-12 with or without interleukin-2 in patients with refractory or recurrent neuroblastoma.
II. Determine, preliminarily, the antitumor effect of interleukin-12 with or without interleukin-2 in these patients.
III. Evaluate the immunoregulatory activity of interleukin-12 with or without interleukin-2 in these patients.
IV. Evaluate the antiangiogenic activity of interleukin-12 with or without interleukin-2 in these patients.
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
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of neuroblastoma
- •Histologically confirmed disease AND/OR disease defined by tumor cells in the bone marrow and elevated urinary catecholamine metabolites
- •Persistent and/or refractory disease, with at least 1 of the following:
- •Biopsy-proven residual disease at least 12 weeks after myeloablative therapy
- •Progressive disease after nonmyeloablative or myeloablative therapy
- •Recurrent disease, evidenced by any of the following:
- •Biopsy-proven recurrent soft tissue disease
- •Metaiodobenzylguanidine (MIBG)-positive lesions visible on any other imaging modality or repeat MIBG obtained 2-4 weeks or more apart
- •Histologically confirmed bone marrow disease
- •Progressive or stable disease after at least 1 prior standard salvage regime
- •No clinically significant pleural effusion
- •Life expectancy >= 12 weeks
- •Hepatitis A antibody negative
- •Hepatitis B surface antigen negative
- •Positive hepatitis B titer allowed if patient has been immunized and has no history of disease
- •Hepatitis C virus negative
- •No history of congenital or acquired coagulation disorder
- •Cardiac function normal by ECG
- •No dyspnea at rest
- •No exercise intolerance
- •Oxygen saturation at least 94% by pulse oximetry
- •DLCO greater than 60% of predicted
- •FEV1 greater than 70% of predicted
- •Negative pregnancy test
- •Skull-based bony lesions without space-occupying intracranial extension are allowed
- •No prior or concurrent intracranial metastatic disease to the brain parenchyma
- •Not pregnant or nursing
- •Fertile patients must use effective barrier contraception during and for at least 2 months after study
- •No prior hematologic malignancy (including leukemia or lymphoma)
- •No history of malignant hyperthermia
- •No prior or concurrent autoimmune disease
- •No positive direct Coombs testing
- •No history of ongoing or intermittent bowel obstruction
- •No active infection or other significant systemic illness
- •More than 2 weeks since prior fenretinide
- •More than 2 weeks since prior 13-cis-retinoic acid
- •More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
- •More than 2 weeks since prior interferons or interleukins
- •More than 2 weeks since prior cytokine-fusion proteins
- •More than 2 weeks since prior IV immunoglobulin (IVIG)
- •No prior interleukin-12
- •No concurrent cytokines
- •No concurrent fenretinide
- •No concurrent 13-cis-retinoic acid
- •No other concurrent immunomodulators, including:
- •G-CSF and GM-CSF
- •Interferons
- •Other interleukins
- •More than 4 weeks since prior chemotherapy
- •No other unstable medical condition or critical illness that would preclude study participation
- 另有 23 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (IL-12, aldesleukin)
Cohort A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12.
Cohort B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A.
Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator.
Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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.
Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD.
干预措施: aldesleukin (Biological)
Treatment (IL-12, aldesleukin)
Cohort A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12.
Cohort B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A.
Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator.
Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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.
Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD.
干预措施: recombinant interleukin-12 (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)
时间窗: 28 days
次要结局
- Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST)(Up to 3 weeks)