Phase II Feasability Study Using ch14.18/CHO Antibody and Subcutaneous Interleukin 2 After Haploidentical Stem Cell Transplantation in Children With Relapsed Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 4
- 主要终点
- Success of treatment
研究概览
简要总结
A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m²) for five consecutive days will be administered every 4 weeks, starting 60-180 days after previous haploidentical stem cell transplantation.
Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year
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
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Less than or equal to 21 years of age.
- •Histologically confirmed neuroblastoma.
- •Refractory to standard treatment (i.e. refractory disease) or relapse after previous autologous or allogenic stem cell transplantation.
- •Patient has undergone haploidentical stem cell transplantation prior to antibody infusion according to appendix IV at least 60 days prior to starting immunotherapy.
- •Serum glutamate pyruvate transaminase (SGPT) less than 2.5 times the upper limit of normal for age and total bilirubin less than 2 times the upper limit of normal for age. D-Dimers less than 2 times the upper limit of normal.
- •Creatinine clearance or radioisotope GFR greater than or equal to 40 ml/min/1.73m
- •Cardiac shortening fraction greater than or equal to 20% by echocardiogram. Karnofsky/Lansky performance score (age appropriate) of greater than or equal to
- •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.
- •Written informed consent is obtained, and for minors a written agreement by parents or legal guardian.
排除标准
- •Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval > 450 milliseconds).
- •Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.
- •Patients with significant psychiatric disabilities or uncontrolled seizure disorders.
- •Patients with active infections or active peptic ulcer, unless these conditions are corrected or controlled.
- •Patients with acute GvHD Grade III or IV or extensive chronic GvHD.
- •Patients with clinically significant, symptomatic, pleural effusions.
- •Patients who have had major surgery, (i.e. laparotomy or thoracotomy) within the past two weeks.
- •Patients who will more than 12 months post haploidentical stem cell transplantation at the time of starting the first cycle of immunotherapy.
- •Prior administration of ch14.18 antibody after allogeneic stem cell transplantation (prior administration after autologous transplantation will be acceptable)
- •HIV or Hepatitis B Surface (HBS) Ag positive. As presence of either may influence the ability if the immune system to be stimulated by this treatment.
研究组 & 干预措施
ch14.18
A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m² ) for five consecutive days will be administered every 4 weeks.
Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year.
干预措施: ch14.18/CHO (Drug)
结局指标
主要结局
Success of treatment
时间窗: 180 days
Primary endpoint is "success of treatment" defined as a patient receiving the full protocol treatment, still alive 180 days after treatment without progression and without unacceptable toxicity and acute GvHD \>= Grade III or extensive chronic GvHD. Thus, a composite variable is used as primary endpoint: Treatment success, is defined as a patients who did not experience 1. unacceptable toxicities 2. acute GvHD \>= Grade III or extensive chronic GvHD 3. other toxicities that did not recover to \<= Grade 1 within 4 weeks or 4. progressive disease after 6 cycles or 5. deaths within treatment after SCT 6. withdrawal due to other reasons
次要结局
- Anti tumour responses(1 year)
- Pharmakoinetics(1 Year)
- NK Cell aktivation and proliferation(1 Year)
研究者
Peter Lang
Head of stem cell transplantation unit
University Children's Hospital Tuebingen