A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 19
- 主要终点
- Percentage of Participants With Unacceptable Toxicity
研究概览
简要总结
This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Sargramostim helps the body produce normal infection-fighting white blood cells. These cells also help the dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab and sargramostim with combination chemotherapy may work better than combination chemotherapy alone in treating patients with high-risk neuroblastoma.
详细描述
PRIMARY OBJECTIVE:
I. To assess the feasibility and tolerability of administering ch14.18 (dinutuximab) and sargramostim (GM-CSF) in combination with a multi-agent chemotherapy regimen during cycles 3-5 of the Induction phase for patients with newly-diagnosed high-risk neuroblastoma.
SECONDARY OBJECTIVE:
I. To describe the response rates, event-free survival (EFS) and overall survival (OS) for patients receiving the combination of standard Induction chemotherapy and ch14.18 (dinutuximab) followed by tandem transplant, radiation therapy, and post-consolidation immunotherapy.
EXPLORATORY OBJECTIVES:
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 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P
- •Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. The following disease groups are eligible:
- •Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
- •MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features; OR
- •Age > 547 days regardless of biologic features;
- •Patients with INRG stage MS disease with MYCN amplification
- •Patients with INRG stage L2 disease with MYCN amplification
- •Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progress to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M.
- •Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M.
- •Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing as described).
- •Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible.
- •Patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
- •Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
- •Age 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)
- •Age 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)
- •Age 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
- •Age 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
- •Age 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
- •Age 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
- •Age 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
- •Age >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN. For the purposes of this study, ULN for ALT is 45 IU/L (within 7 days prior to enrollment).
- •Shortening fraction of >= 27% by echocardiogram (within 7 days prior to enrollment).
- •Ejection fraction of >= 50% by echocardiogram or radionuclide angiogram (within 7 days prior to enrollment).
- •No known contraindication to peripheral blood stem cell (PBSC) collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
- •All patients and/or their parents or legal guardians must sign a written informed consent.
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
排除标准
- •Patients >18 months of age with INRG stage L2, MYCN non-amplified, regardless of additional biologic features.
- •Patients with bone marrow failure syndromes.
- •Patients that are >= 12 and =< 18 months of age with INRG stage M and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid [DNA] index > 1) are not eligible.
- •Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine, corticosteroids for reasons other than prevention/treatment of allergic reactions, adrenal replacement therapy, etc.) are not eligible.
- •Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- •Lactating females who plan to breastfeed their infants.
- •Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method during study therapy and for two months after the last dose of ch14.18 (dinutuximab) are not eligible.
研究组 & 干预措施
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Carboplatin (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Cisplatin (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Dinutuximab (Biological)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Dexrazoxane (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: External Beam Radiation Therapy (Radiation)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Etoposide (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Isotretinoin (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Sargramostim (Biological)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Melphalan (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Thiotepa (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Topotecan (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Vincristine (Drug)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Percentage of Participants With Unacceptable Toxicity
时间窗: Up to the first 5 cycles of treatment
Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.
Percentage of Participants Who Are Feasibility "Failure"
时间窗: Up to the first 5 cycles of treatment
Feasibility "failures" were defined as patients that did not receive \>= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility "failure" rate together with a 95% confidence interval.
次要结局
- Event-free Survival(Up to 1 year)
- Response Rate(Up to the first 5 cycles of treatment)
- Overall Survival(Up to 1 year)