Phase II Single Arm Study to Assess Dinutuximab (Ch 14.18) Combined With the Cytokines Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) and IL-2 in Patients With High-risk Neuroblastoma Not Eligible to Other Immunotherapy Trials
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants with Serious and Non-Serious Adverse Events
研究概览
简要总结
The purpose of this study is to evaluate safety of the triple COG schema with the monoclonal antibody Dinutuximab + cytokines (GM-CSF and IL2) and isotretinoin (13-cis-retinoic acid, or RA) in patients with high-risk neuroblastoma.
详细描述
Assess toxicity and safety of subcutaneous GM-CSF and iv IL-2 in enhancing Dinutuximab-mediated ablation of Bone Marrow (BM) disease in patients with high-risk neuroblastoma who have achieved a Complete Response or Very Good Partial Response of the macroscopic disease in the investigators institution.
Assess response of minimal residual disease (MRD) of the anti-GD2 monoclonal antibody Dinutuximab combined with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-2 in patients with high-risk neuroblastoma (NB). More precisely, to apply real-time quantitative RT-PCR to test the hypothesis that minimal residual disease content of BM after the first treatments with dinutuximab/GM-CSF has significant prognostic impact on relapse-free survival.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of neuroblastoma as defined by international criteria by histopathology or bone marrow metastases. Patients age must be less than 18 years at the time of initial diagnosis.
- •Neuroblastoma, as defined by risk-related treatment guidelines and the International Neuroblastoma Staging System, stage 4 with (any age) or without (>18 months) MYCN-amplification, or MYCN-amplified neuroblastoma other than stage 1, or high-risk neuroblastoma defined based on the 3-gene molecular profile developed at our institution (Garcia I, et al. CCR 2012).
- •Group 1 patients have neuroblastoma (as defined above) resistant to standard therapy, as evidenced by incomplete response in bone marrow, but no MIBG-avid soft tissue or bone tumor and no progressive disease.
- •Group 2 patients have no evidence of measurable disease
- •3 - Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of > 2 months.
- •4- Pre-enrollment tumor survey: Prior to enrollment a determination of residual disease must be Performed (Tumor imaging studies including CT or MRI, MIBG scan, bone marrow aspiration & biopsy, and blood and bone marrow samples). This disease assessment is required for eligibility.
- •5 - Patients must have adequate organ functions at the time of registration:
- •Hematological: Total absolute phagocyte count (APC = neutrophils + monocytes) is at least 1000/microL
- •Renal: Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2 or serum creatinine based on age/gender.
- •Hepatic- total bilirubin < 1.5 x normal, and SGPT (ALT) < 5 x normal. Veno-occlusive disease, if present, should be stable or improving.
- •Cardiac- shortening fraction of > 30% by echocardiogram, or if shortening fraction abnormal, ejection fraction of > 55% by gated radionuclide study.
- •Pulmonary- FEV1 and FVC > 60% of predicted by pulmonary function test. For children who are unable to do PFTs, no evidence of dyspnea at rest, no exercise intolerance.
- •Central nervous system- Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled. CNS toxicity < Grade
- •6 - Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
- •7 - Signed informed consent indicating awareness of the investigational nature of this program.
排除标准
- •Existing severe major organ dysfunction, i.e., renal., cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade
- •Progressive disease or MIBG-avid soft tissue/bone tumor.
- •Active life-threatening infection.
- •Inability to comply with protocol requirements.
- •Patient is eligible for SIOP HR-NB-01 protocol (= newly diagnosed high-risk neuroblastoma patient in a center where the SIOP protocol is open for enrollment).
研究组 & 干预措施
Dinutuximab. Immunotherapy
Dinutuximab will be administered at 17.5 mg/m2/day for 4 days up to 5 courses. Each dose should be infused IV over approximately 10 hours.
Immunotherapy (sargramostim + isotretinoin + interleukin2) Sargramostim will be administered at 250 micrograms/m2/d by subcutaneous (SC) injection daily from Day 0 through 13 (daily with the infusion of Dinutuximab and for 3 days before and 7 days afterward).
Isotretinoin (13-cis-retinoic acid, or RA) (160mg/m2/day or 5.33mg/kg/day if < 12kg) PO divided into 2 doses daily x 14 days.
Interleukin-2 (IL-2) 3 MIU/m2/day will be given by continuous infusion for 4 days during the first week of each course 2 and 4 given on Days 0 - 3
干预措施: Dinutuximab. Immunotherapy (Drug)
结局指标
主要结局
Number of Participants with Serious and Non-Serious Adverse Events
时间窗: Expected, 7 months from treatment initiation. From IC signature, every day during immunotherapy treatment (Cycles 1 to 5), day 1 of cycle 6. From patient consent signature up to 30 days after administration of the last dose of study drug.
Type, incidence, severity, timing, seriousness, and relatedness; of reported AEs, physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.
次要结局
- Relapse-free survival(Anticipated, 2 years from study treatment initiation. From IC signature, every 3 months, up to 2 years (anticipated).)