A Phase I/II Study Using Allogeneic Tumor Cell Vaccination With Oral Metronomic Cytoxan in Patients With High-Risk Neuroblastoma (ATOMIC)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
Neuroblastoma is the second most common solid tumor seen in children, but causes approximately 15% of childhood cancer deaths each year. Patients with high-risk disease require treatment with a combination of chemotherapy, surgery, radiation, and stem cell transplant; however, many will have their disease come back within 3 years. Due to this high rate of relapse, this study is being done to investigate an experimental treatment option for children whose disease has returned.
This clinical trial is for patients with neuroblastoma that has either come back after treatment or never went away in the first place. A series of immunizations will be administered using a tumor vaccine and add low-dose chemotherapy to be taken by mouth on a daily basis. The hope is that the vaccine will cause the immune system to recognize and kill more types of neuroblastoma tumors. Additionally, the immunizations will be combined with daily low dose chemotherapy. Daily low-dose chemotherapy, also know as metronomic chemotherapy, works by attacking the blood vessels that allow tumors to grow. Using metronomic doses of a drug called cytoxan can also decrease T regulatory cells, a specific type of cell that tumors use to hide from the immune system.
The purpose of this study is to test the safety and anti-tumor effect of the tumor cell vaccination plus low dose, metronomic chemotherapy in treating patients with relapsed/refractory neuroblastoma.
详细描述
WHAT IS THE OVERALL TREATMENT PLAN AND HOW MANY VACCINATIONS WILL THE PATIENT RECEIVE? There will be several injections of the vaccine scheduled. The first injection will be given 3 days after starting oral cytoxan. The 2nd to 4th injections will be given approximately every 14 days after the previous vaccine. During this time, the patient will be taking oral cytoxan once a day except on the day of and 4 days following the vaccine. Two to 3 weeks after the 4th vaccine, the patient will have a complete evaluation of their disease. If the scans and lab tests show that the patient has not had any serious side-effects, they will be eligible to receive 4 additional vaccinations given at 3 week intervals. The disease will be re-evaluated again after vaccine numbers 6 and 8. If the patient is able to complete the entire study, they will have received a total of 8 vaccinations and the last dose of oral cytoxan will be 1 month after the 8th vaccination. Total time duration for participating in this study is 15 years (treatment portion within year 1 and follow up during years 2-15).
Neuroblastoma vaccinations are given like many other vaccines. They will be given subcutaneously. The injections will be 1/10th of a teaspoon.
MEDICAL TESTS BEFORE STARTING TREATMENT:
Before starting low dose chemotherapy plus oral cytoxan, patients will receive a series of standard medical tests:
- Physical exam
- Blood tests to measure blood cells, blood salts, kidney and liver function
- Measurements of their disease (CT or MRI of the primary tumor site and any locations of tumor spread; MIBG or Bone scan; Chest X-ray if they did not have a CT of the chest; and bone marrow studies if the patient has known bone marrow disease)
- Baseline testing of immune function
- Pregnancy testing will be performed on females of child bearing age
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
- •Histologically proven high risk neuroblastoma in first or subsequent relapse or with primary refractory disease or inability to complete standard therapy
- •Age less than 21 at time of initial diagnosis
- •Life expectancy 12 weeks or greater
- •Karnofsky or Lansky score of 50 or greater
- •Platelet count of 50,000/ul or greater
- •ANC greater than 750/ul
- •Alk Phos level less than 2.5 x upper limit of normal
- •Bilirubin less than 2x normal
- •AST less than 3x normal
- •Hgb 8.0 or greater
- •Creatinine 2 x ULN or less OR GFR greater than 40 ml/min/1.73 m2
- •Patient has recovered from last chemotherapy or investigational therapy prior to study enrollment
- •Women of child-bearing potential must not be pregnant and take/use effective birth control while participating in the study.
排除标准
- •Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research
- •Women who are breast-feeding
- •Known HIV positive subjects since treatment may be immunosuppressive
- •Severe intercurrent infection or uncontrolled condition including, but not limited to ongoing or active infection, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Previous use of oral cytoxan for more than 2 consecutive months within the last 6 months
- •Patients currently receiving any investigational agents or have received any tumor vaccines within the previous six months
- •Patients, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
研究组 & 干预措施
Treatment Plan
Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells) and Cytoxan (Cyclophosphamide)
干预措施: Cytoxan (Drug)
Treatment Plan
Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells) and Cytoxan (Cyclophosphamide)
干预措施: Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells (Biological)
结局指标
主要结局
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
时间窗: week 30
Phase I Primary Objective: Evaluate the safety of fixed dose oral cytoxan administered metronomically to coincide with repeated immunizations of gene-modified, IL-2/lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-LTN cells co-administered with unmodified SKNLP neuroblastoma cell lines in patients with a history of relapsed/refractory high-risk neuroblastoma.
次要结局
- Participants with T-cell changes as a Measure of Immune Response(15 years)
- Number of Participants with Disease Progression as a Measure of Efficacy(10 weeks)
研究者
Malcolm Brenner
Principal Investigator
Baylor College of Medicine