NCT04560166终止2 期
Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination With Irinotecan and Temozolomide in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. An International, Single-Arm, Multicenter Phase 2 Trial.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 3
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
An International, Single-Arm, Multicenter Phase 2 Trial.
详细描述
This is an international, single-arm, multicenter phase 2 trial, in patients ≥ 12 months of age with high-risk NB with primary refractory disease or in first relapse. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. The Follow-Up period ends 2 years after End of Treatment.
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
- 12 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neuroblastoma (NB)
- •Documented high-risk disease
- •Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids)
- •Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following:
- •verified first progression during multi-drug frontline treatment or
- •verified first episode of relapse, defined as recurrence after response to frontline treatment, or
- •verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score ≥3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above
- •The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment:
- •Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan
- •MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction
- •Age ≥ 12 months at enrollment
- •Written informed consent
排除标准
- •Myelodysplastic syndrome or any malignancy other than NB
- •Any systemic anti-cancer therapy within 3 weeks
- •Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator
- •Therapeutic 131I-MIBG within 6 weeks prior to enrollment
- •Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response
- •Prior treatment with anti-GD2 if the patient experienced Progressive Disease (PD) while on anti-GD2 treatment
- •Receipt of second line chemotherapy after designation of primary refractory disease or first relapse or PD
- •NB in Bone Marrow (BM) only
- •NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment
- •Performance status of < 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (for patients aged 16 years or older)
- •Life expectancy of less than 6 months
- •Left ventricular ejection fraction < 50% by echocardiography
- •Inadequate pulmonary function
- •Diarrhea Grade ≥ 2
- •Treatment with long-acting myeloid growth factor within 14 days or short-acting myeloid growth factor within 7 days prior to first dose of GM-CSF
- •Receipt of immunosuppressive treatment (local steroids excluded) within 4 weeks prior to enrollment
- •Life threatening infection(s)
- •Uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment)
- •Treatment with enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to enrollment
- •Concomitant use with St John's wort
- •Allogeneic hematopoietic stem cell transplantation (allo-SCT) or donor-lymphocyte-infusion (defined as any kind of active allogeneic lymphocyte suspension)
- •Treatment with Hematopoietic Progenitor Cell (HPC) boost within 2 months prior to enrollment
- •History of allergy or known hypersensitivity to GM-CSF, yeast-derived products, or any component of GM-CSF, naxitamab, irinotecan or temozolomide
- •History of anaphylactic reactions CTCAE Grade 4 related to prior anti-GD2 antibody therapy
- •Unacceptable hematological status at screening, defined as one of the following:
- •Hemoglobin <5.0 mmol/L (<8 g/dL)
- •White blood cell count <1000/µL
- •Absolute neutrophil count <750/µL
- •Platelet count < 75,000/µL
- •Unacceptable liver function at screening, defined as one of the following:
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >5 times upper normal limit (UNL)
- •Total bilirubin >1.5 x UNL
- •Unacceptable kidney function at screening, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation
- •Inability to comply with protocol
- •Significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of trial agents or to significantly increase the severity of the toxicities experienced from trial treatment
- •Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods
研究组 & 干预措施
Naxitamab and GM-CSF in combination with irinotecan and temozolomide
Experimental
A treatment cycle is 21 days. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10).
Patients will receive up to 18 IT cycles after enrollment. Naxitamab and GM-CSF will be given for at least 8 cycles.
干预措施: Naxitamab and GM-CSF in combination with irinotecan and temozolomide (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 84 days
The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC)
次要结局
未报告次要终点
研究者
研究点 (3)
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