CLINICAL TRIAL: PI TRIAL OF IMMUNOSTIMULATION JVRS-100 FOR RELAPSED OR REFRACTOR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项评估JVRS-100的安全性和耐受性的I期方案，JVRS-100是一种阳离子脂质DNA复合体(CLDC)，用于治疗复发/难治性白血病患者。目前，这种疾病的预后令人沮丧。JVRS-100由阳离子脂类和不含基因插入的质粒DNA(非编码DNA)组成的复合体，是天然免疫和获得性免疫的有效激活剂，诱导NK、T和B细胞激活，并刺激干扰素、干扰素和IL-12等细胞因子的分泌。这是一个2阶段的I期试验。在第一阶段，将遵循加速滴定方案，每个剂量水平有一名患者。第二阶段将在第一阶段观察到剂量限制毒性(DLT)或达到第一阶段的最大剂量后开始。第二阶段将遵循改进的斐波纳契方案，每个剂量水平有3-6名受试者，直到确定推荐的第二阶段剂量(RP2D)。然后，队列将扩大到最多12名患者，以更全面地评估RP2D。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase I protocol to evaluate the safety and tolerability of JVRS-100, a cationic lipid DNA complex (CLDC), for the treatment of patients with relapsed/refractory leukemia. This currently has a dismal prognosis. JVRS-100 consists of complexes of cationic lipid and plasmid DNA without a gene insert (non-coding DNA) which are potent activators of innate and adaptive immunity, induce NK, T and B cell activation, and stimulate the secretion of interferon-¿, interferon-¿, IL-12 and other cytokines. This is a 2 stage Phase I trial. In stage 1, an accelerated titration schema will be followed with one patient at each dose level. Stage 2 will commence after a dose limiting toxicity (DLT) is observed in stage 1 or after the maximum dose for stage 1 is reached. Stage 2 will follow a modified Fibonacci schema with 3-6 subjects at each dose level until a Recommended Phase 2 Dose (RP2D) is determined. The cohort will then be expanded to a maximum of 12 patients to more fully evaluate the RP2D.