Phase I/II Study of Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- maximum tolerated dosage
研究概览
简要总结
The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is safe for treating neuroblastoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
- •Patients must have high-risk NB (including MYCNamplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age) AND:
- •Phase I: Patients must have refractory or relapsed NB, resistant to standard therapy*.
- •*For NB, standard therapy includes intensive induction chemotherapy, followed by a variety of consolidation or salvage therapies, depending on response.
- •Phase II: Patients must have primary or secondary refractory disease in BM, defined as morphologic evidence of NB in BM and/or abnormal 123I-MIBG uptake in osteomedullary sites, OR patients patients in ≥ 2nd CR patients are in ≥2nd CR
- •Patients must be older than 1 year of age.
- •Prior treatment with murine and humanized 3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody (HAMA) positivity is allowed.
- •White blood cell count ≥1000/ul (phase I only)
- •Absolute neutrophil count ≥500/ul (phase I only)
- •Absolute lymphocyte count ≥500/ul (phase I only)
- •Platelet count ≥25,000/ul (phase I only)
- •No chemotherapy or immunotherapy for a minimum of three weeks prior to start of hu3F8
- •Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment
- •Signed informed consent indicating awareness of the investigational nature of this program.
排除标准
- •Existing major organ dysfunction > grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets).
- •Active life-threatening infection.
- •Pregnant women or women who are breast-feeding.
- •Inability to comply with protocol requirements, including PK studies and genetic studies (phase I only)
- •History of allergy to mouse proteins.
- •Positive human anti-hu3F8 antibody (HAHA) titer
研究组 & 干预措施
Hu3F8 with GM-CSF
The phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. The expansion phase II single arm trial assesses the anti-NB activity of hu3F8+GM-CSF.in 3 groups of patients: Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123I-MIBG scan. Group 2 patients are in ≥2nd CR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123I-MIBG scan. Ph II: Groups 1 & 3 pts can continue to get cycles every 1-2 months for up to 24 months from study enrollment or until they receive 5 cycles after a major response (CR or PR) is achieved.
干预措施: Hu3F8 With GM-CSF (Biological)
expansion phase II single arm trial
Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123^I-MIBG scan. Group 2 patients are in >2nd CR/VGPR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123^I-MIBG scan. GM-CSF can be omitted if patients have a history of an allergy to GM-CSF or develop an allergic reaction to GM-CSF after initiating therapy while on the protocol.
干预措施: Hu3F8 With GM-CSF (Biological)
结局指标
主要结局
maximum tolerated dosage
时间窗: 1 year
hu3F8 when combined with GM-CSF. DLT is defined after 1 cycle. Seventeen dosage levels of hu3F8 will be tested with three to six patients at each dosage level.
assess the toxicity
时间窗: 1 year
of the humanized anti GD2 antibody hu3F8 when combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in patients with high risk neuroblastoma. All observed adverse events, regardless of treatment group or suspected causal relationship to study drug will be recorded. Adverse events will be identified and graded using the Common Toxicity Criteria Version 4.0
次要结局
- pharmacokinetics of hu3F8(1 year)
- assess activity of hu3F8 plus GM-CSF against HR-NB(2 years)
- quantitate the response of marrow NB(1 year)