Phase 1/2 Open-Label, Multiple-dose, Dose-escalation Study to Evaluate the Safety and Tolerability of IMO-8400 in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 10
- 主要终点
- Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia
研究概览
简要总结
Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 90% of the patients with Waldenström's macroglobulinemia. MYD88 is a key linker protein in the signaling pathway of Toll Like Receptors (TLRs) 7, 8, and 9, and IMO-8400 is an oligonucleotide specifically designed to inhibit TLRs 7,8, and 9. The scientific hypothesis for use of IMO-8400 to treat patients with Waldenström's macroglobulinemia depends on the inhibition of mutant MYD88 signaling in the TLR pathway, thereby interrupting the proliferation of cell populations responsible for the propagation of the disease.
详细描述
Eligible subjects will be enrolled and assigned to escalating dose cohorts. Treatment will be administered by subcutaneous injection.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a diagnosis of relapsed Waldenstrom's Macroglobulinemia.
- •In addition to the above, key inclusion and exclusion criteria are listed below.
- •Inclusion Criteria:
- •At least 18 years of age.
- •Agree to use contraception
- •Hemoglobin ≥ 7.5 g/dL, - Absolute neutrophil count ≥ 1.0 x 109/L (1000/mm3), - Platelets ≥ 50,000/μL
排除标准
- •Is nursing or pregnant
- •Has BMI > 34.9 kg/m
- •Has a positive test for human immunodeficiency virus (HIV-1 or -2) hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg).
- •Receiving chronic systemic corticosteroid therapy > 20 mg of prednisone daily.
- •Being treated with other anti-cancer therapies (approved or investigational).
- •Has, at the initiation of study drug, received cytotoxic chemotherapy or a Bruton's tyrosine kinase (BTK)-inhibitor (e.g. ibrutinib) within the past 3 weeks or rituximab within the past 2 months
- •Has an active infection requiring systemic antibiotics.
- •Has had surgery requiring general anesthesia within 4 weeks of starting the study.
- •Has autoimmune cytopenia (anemia, thrombocytopenia, leukopenia).
- •Has heart failure of Class III or IV.
- •Has sensory or motor neuropathy limiting daily activities.
研究组 & 干预措施
IMO-8400 at escalating dose levels
IMO-8400 at escalating dose levels by subcutaneous injection
干预措施: IMO-8400 (Drug)
结局指标
主要结局
Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia
时间窗: Up to 24 weeks
Safety and tolerability of IMO-8400 in patients with Waldenstrom's Macroglobulinemia: Assessment of adverse events
次要结局
- Best Overall Response(Up to 24 weeks)
- Identify the Number of Patients Experiencing DLTs at Each Dose Level(28 days)
- Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection - Cmax.(Cycle 1 Week 1 Day 1: Samples were obtained pre-dose (within 1 hr prior to injection) and post-dose at 1 hr (+/-5 min), 2 hrs (+/-10 min) and 4 hrs (+/-15 min))
- Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection - AUC0-t (hr*ng/mL)(Cycle 1 Week 1 Day 1: Samples were obtained pre-dose (within 1 hr prior to injection) and post-dose at 1 hr (+/-5 min), 2 hrs (+/-10 min) and 4 hrs (+/-15 min))