Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) When Combined With Interleukin-2 in Patients With High-Risk Neuroblastoma and GD2-positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 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 "humanized 3F8" (Hu3F8) when combined with interleukin-2 (rIL2) is safe for treating neuroblastoma and other cancers. A phase 1 study means the investigators are trying to find out what side effects happen when higher and higher doses of a drug are used.
The investigators want to find out what effects, good and/or bad, Hu3F8 combined with rIL2 has on cancer. The amount of Hu3F8 that patients gets will depend on when they start treatment on this study. The amount of rIL2 will be the same for all patients. The investigators also want to find out more about how Hu3F8 works and how effective it is in attacking the disease when combined with rIL2.
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
- 13 Months 至 —（Child, Adult, Older Adult）
- 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,84 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels, or (2) a tumor that is GD2-positive.
- •o A non-NB tumor is defined as GD2-positive by immunostaining with m3F
- •If fresh or frozen tumor is not available for immunostaining, patients will be considered eligible if published reports show that >50% of that tumor type is GD2-positive by immunohistochemistry. (Note: Tissues must be fresh/frozen as fixed, paraffin-embedded specimens are unsuitable for anti-GD2 immunostaining). Tumors known to be GD2- positive by this criteria do not need immunostaining. These include: Melanoma (>50%), Desmoplastic small round cell tumors (70%), Osteosarcoma (88%) and Soft tissue sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma (93%).
- •Patients must have either (1) refractory or relapsed high-risk NB (including MYCN-amplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age)resistant to standard therapy*, or (2) refractory or relapsed GD2-positive tumor after receiving available life-prolonging therapies.
- •*For NB, standard therapy generally includes 5-8 cycles of high dose induction chemotherapy followed by resection of gross residual tumor, with or without myeloablative chemotherapy with peripheral blood stem cell rescue and radiation therapy to the primary site. There are also salvage chemotherapy regimens for residual disease after standard induction therapy or for relapsed NB. Some examples of these chemotherapy combinations are: high-dose cyclophosphamide, topotecan and vincristine; high-dose cyclophosphamide, irinotecan and vincristine; irinotecan and temozolomide; or ifosfamide, carboplatin and etoposide.
- •Patients must be older than 1 year of age.
- •Prior treatment with murine 3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have HAHA antibody titer less than or = to 1300 Elisa units/ml
- •White blood cell count ≥1000/ul
- •Absolute neutrophil count ≥500/ul
- •Absolute lymphocyte count ≥500/ul
- •Platelet count ≥25,000/ul
- •No chemotherapy or immunotherapy for a minimum of three weeks prior to study enrollment
- •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).
- •Hematologic and primary CNS malignancies
- •Active life-threatening infection.
- •Pregnant women or women who are breast-feeding.
- •Inability to comply with protocol requirements.
研究组 & 干预措施
hu3F8 and rIL-2
This phase I single arm trial assesses the toxicity of escalating doses of hu3F8 (day 1 and day 8) in the presence of 6 × 10^6 U rIL-2/m^2/d x 5 days sc (day 8 through day 12). These 2 doses of hu3F8 and 5 doses of rIL-2 constitute a treatment cycle.
干预措施: 3F8 Monoclonal Antibody Combined with Interleukin-2 (Drug)
结局指标
主要结局
maximum tolerated dosage
时间窗: 1 year
of hu3F8 when combined with rIL-2. six dosage levels of hu3F8 will be tested with three to six patients at each dosage level.
次要结局
- quantification of pain(1 year)
- pharmacokinetics(1 year)
- anti-tumor activity(1 year)
- biologic correlates with hu3F8 dose(1 year)