Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M (ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplant (HCT)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- AlloVir
- 入组人数
- 97
- 试验地点
- 56
- 主要终点
- Time to Resolution of Macroscopic Hematuria
研究概览
简要总结
Study to Evaluate Viralym-M (ALVR105) for the Treatment of Virus-Associated Hemorrhagic Cystitis (HC).
详细描述
The study hypothesis is that the administration of posoleucel (ALVR105) to patients with virus-associated HC will demonstrate superiority for the time to resolution of HC (as measured by resolution of macroscopic hematuria) compared to patients treated with placebo. The primary hypothesis will be tested in patients with BK virus (BKV) viruria to demonstrate superiority over placebo in this population (BK Intent-to-Treat [ITT] Population). A supplementary analysis will be conducted in all patients with any virus-associated HC (cytomegalovirus [CMV], human herpesvirus 6 [HHV-6], Epstein-Barr virus [EBV], JC virus [JCV], and/or adenovirus [AdV]) in order to evaluate efficacy in this broader population (ITT Population).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria in order to be eligible to participate in the study:
- •Male or female ≥1 year of age.
- •Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior to randomization.
- •Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm³ for 3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm³ at the time of randomization.
- •Diagnosed with HC based on the following criteria (all 3 criteria must be met):
- •Clinical signs and/or symptoms of cystitis.
- •Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots.
- •Viruria with ≥1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
- •At least 1 identified, suitably matched posoleucel (ALVR105) cell line for infusion is available.
排除标准
- •Participants who meet any of the following criteria will be excluded from participation in the study:
- •Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
- •Therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization.
- •Evidence of active Grade >2 acute graft versus host disease (GVHD).
- •Uncontrolled or progressive bacterial or fungal infections.
- •Uncontrolled or progressive viral infections not targeted by posoleucel (ALVR105).
- •Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
- •Known or presumed pneumonia secondary to any organism that is not considered to be well-controlled by antimicrobial therapy.
- •Pregnant or lactating or planning to become pregnant.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Posoleucel (ALVR105)
Administered as 2-4 milliliter infusion, visually identical to placebo
干预措施: Posoleucel (ALVR105) (Biological)
Placebo
Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)
干预措施: Placebo (Biological)
结局指标
主要结局
Time to Resolution of Macroscopic Hematuria
时间窗: Up to 24 weeks
Time to macroscopic hematuria resolution is calculated from time of randomization to the first date of observed macroscopic hematuria resolution. Kaplan-Meier estimates reported as median number of days to resolution. Participants were censored at the last follow-up time of any participant in the ITT population if they took definitive therapies to stop bladder bleeding or received treatment for hemorrhagic cystitis with non-PSL VSTs before achieving resolution or deceased. Participants were also censored at last follow up if they failed to achieve resolution by end of study.
次要结局
- Number of Participants With Treatment Emergent Cytokine Release Syndrome (CRS)(Up to 24 weeks)
- Average Daily Bladder Pain(Until event occurrence through Week 6)
- Time Until Bladder Pain is Resolved(Until event occurrence through Week 24)
- Days in the Hospital for Any Reason(Until event occurrence through Week 24)
- Number of Participants With Treatment Emergent Acute Graft Versus Host Disease (GVHD)(Up to 24 weeks)
- Time to Resolution for All Target Viruses(Until event occurrence through Week 24)