NCT03860207终止1 期
Phase I/II Study of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma, and Other GD2(+) Solid Tumors
适应症
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities (DLTs) Phase I
研究概览
简要总结
The purpose of this study is to test the safety of a study drug called humanized 3F8 bispecific antibody (Hu3F8-BsAb).
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 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have either (1) a diagnosis of NB as defined by international criteria,i.e.,histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels, or (2) high grade osteosarcoma verified by histopathology (confirmed by the MSKCC Department of Pathology), or (3) other GD2-expressing solid tumor.
- •For tumors other than NB and osteosarcoma, only tumors known to be GD2 positive are eligible: melanoma, desmoplastic small round cell tumors, retinoblastoma, medulloblastoma, and soft tissue sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma. Patients with medulloblastoma are eligible only if they have metastatic disease outside the CNS (e.g. in the bone marrow)
- •NB patients must have chemorefractory (e.g. refractory to standard induction chemotherapy including cyclophosphamide, vincristine, cisplatin, etoposide) or relapsed high-risk (HR) neuroblastoma. HR NB is defined as MYCN-amplified stage 3/4/4S of any age, or MYCNnonamplified stage 4 in patients > 18 months of age at diagnosis.
- •Osteosarcoma patients must have relapsed or refractory osteosarcoma after receiving standard systemic chemotherapy (e.g. combination methotrexate, doxorubicin, and cisplatin [MAP]).
- •For non-NB and non-osteosarcoma tumors known to be GD2(+), patients must have relapsed or refractory disease that is resistant to standard therapy.
- •NB patients must have chemo refractory or relapsed HR NB. HR NB is defined as MYCNamplified stage 3/4/4S of any age, or MYCN-nonamplified stage 4 in patients > 18 months of age at diagnosis.
- •The diagnosis of NB must be defined by international criteria i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels.
- •Patients must have a diagnosis of high grade osteosarcoma defined by histopathology (confirmed by the MSKCC Department of Pathology).
- •Patients must have relapsed or refractory osteosarcoma after receiving standard systemic chemotherapy (e.g. combination methotrexate, doxorubicin, and cisplatin [MAP]).
- •All criteria below are common to both phase I and phase II:
- •Disease status
- •For NB patients, patients must have measurable or evaluable disease (e.g. abnormal findings in computed tomography (CT), magnetic resonance imaging (MRI), metaiodobenzylguanidine (MIBG) scan, or positron emission tomography (PET)) OR morphologic evidence of disease in bone marrow.
- •For osteosarcoma or other GD2(+) solid tumor patients, patients must have measurable disease.
- •Other criteria:
- •Patients must be ≥ 1 year of age ( protocol amendment 1.0-5.0)
- •Patients must be ≥ 1 year of age and < 18 years of age (protocol amendment 6.0-10.0)
- •Patients with prior exposure to anti-GD2 antibodies must have a negative HAHA antibody titer
- •Adequate hematopoietic function defined as:
- •Absolute neutrophil count ≥500/ul
- •Absolute lymphocyte count ≥500/ul
- •Platelet count ≥25,000/ul
- •Negative serum pregnancy test in women of child-bearing potential.
- •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
- •Patients who are in complete remission.
- •Existing severe major organ dysfunction. i.e. renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ Grade 3 except for hearing loss, alopecia, anorexia, nausea, hyperbilirubinemia or hypomagnesemia from TPN, which may be Grade
- •Hematologic and active CNS malignancies including CNS metastasis.
- •Active life-threatening infection.
- •Pregnant women or women who are breast-feeding.
- •Inability to comply with protocol requirements.
- •History of autoimmune disease with potential CNS involvement or a current autoimmune disease.
- •Chemotherapy or immunotherapy within three weeks prior to study enrollment. T-cell based immunotherapies (e.g. CAR-modified T cells, checkpoint inhibitors) should have been completed >6 weeks prior to treatment with hu3F8-BsAb.
结局指标
主要结局
Dose Limiting Toxicities (DLTs) Phase I
时间窗: Days 1 through 28 in cycle 1
Summary of DLTs in DLT evaluable subjects.
次要结局
未报告次要终点
研究者
研究点 (1)
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