Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study
试验速览
- 阶段
- 1 期
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose (MTD) of GD2Bi-aATC
研究概览
简要总结
Previous research has demonstrated that investigators can coat (arm) T cells with a special molecule called GD2 bispecific antibody that will help T cells recognize neuroblastoma and osteosarcoma cells and kill them. This bispecific antibody recognizes GD2, a protein found on almost all neuroblastoma and osteosarcoma cells. The investigators put the GD2 bispecific antibody on T cells and give large numbers of these T cells back to patients. The investigators think that these T cells may have a better chance of killing GD2 expressing tumor cells when they are armed with GD2 bispecific antibody. This trial studies the side effects and best dose of activated T cells armed with GD2 bispecific antibody and how well they work in treating patients with neuroblastoma, osteosarcoma, and other GD2-positive solid tumors.
详细描述
PRIMARY OBJECTIVES:
I. To perform a phase I dose-escalation study in patients with recurrent or refractory neuroblastoma (NB) and other GD2-positive tumors to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) for anti-CD3 x hu3F8 bispecific antibody (GD2Bi)-armed activated T cells (aATC) infused twice a week for a total of eight infusions in combination with daily IL-2 (300,000 IU/m^2/day) and GM-CSF (250 ug/m^2 twice per week) in a standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10^6 cells/kg/infusion dose levels.
II. To conduct a phase II clinical trial to explore efficacy and confirm the toxicity profile of GD2Bi-aATC combined with IL-2 and GM-CSF in a phase II expansion cohort of 22 patients with neuroblastoma (NB) using MTD determined in the phase I.
SECONDARY OBJECTIVES:
I. Evaluate immune responses in the phase I/II trial by sequential monitoring of anti-NB cytotoxicity of peripheral blood lymphocytes and IFN-gamma EliSpots directed at NB lines.
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
- 13 Months 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The study is now in the phase II expansion phase.
- •Inclusion Criteria for phase II:
- •The target tumor is limited to neuroblastoma and the diagnosis should be histologically verified.
- •Patients must have refractory or recurrent malignancy; patient's current disease state must be one for which no known curative therapy is available;
- •Patients should not receive any other experimental or phase 1 therapy within 3 weeks prior to study enrollment and monoclonal antibody therapy within 6 weeks
- •To be eligible for phase I study patients should have primary refractory or relapsed disease as evidenced by:
- •Local tumor recurrence measurable on CT or magnetic resonance imaging (MRI) scans with or without metastatic lesions
- •Refractory bone marrow involvement in patients with NB
- •NB with MIBG-positive skeletal lesions
- •The presence of radiographically measurable disease immediately prior to start of Phase I immunotherapy is not an eligibility requirement in the following situations:
- •In patients with NB who have documented bone marrow (BM) involvement;
- •In patients with NB who have MIBG-positive bony lesion(s);
- •An additional eligibility requirement for phase II study includes the presence of radiographically measurable disease with the exception of MIBG-positive NB or NB with bone marrow involvement:
- •Patients must have a Lansky or Karnofsky performance status score of >= 70
- •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
- •Myelosuppressive chemotherapy: must not have received within 3 weeks of starting immunotherapy (IT)
- •Hematopoietic growth factors: at least 7 days since the last dose of growth factor therapy
- •Immunotherapy: at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody
- •Normal organ function
- •All patients or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are postmenarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 3 months after the last dose of GD2Bi-aATC; breastfeeding women should be excluded
- •Patients who have an uncontrolled infection are not eligible
- •Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
研究组 & 干预措施
Treatment (IL-2, GM-CSF, GD2Bi-aATC)
Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.
干预措施: GD2Bi-aATC (Biological)
Treatment (IL-2, GM-CSF, GD2Bi-aATC)
Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.
干预措施: laboratory evaluations of immune responses (Other)
Treatment (IL-2, GM-CSF, GD2Bi-aATC)
Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.
干预措施: GM-CSF (Biological)
Treatment (IL-2, GM-CSF, GD2Bi-aATC)
Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.
干预措施: IL-2 (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) of GD2Bi-aATC
时间窗: 35 days
Safety of GD2Bi-aATC infusions is evaluated to determine MTD
次要结局
- Anti-tumor activity(Up to 12 months)
- Immune responses after GD2Bi-aATC infusions(Up to 12 months)
研究者
Daniel W. Lee, MD
Principal Investigator
University of Virginia