A Phase II Open-Label Randomized Study of Anti-Viral Antibiotic Therapy With and Without Familial (Maternal) Cytomegalovirus (CMV) Cytotoxic T Lymphocytes (CTLs) in Neonates With Moderate/Severe Maternal Acquired CMV Infection
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- To determine the safety of giving CMV CTLs combined with anti-viral therapy in neonates with CMV
研究概览
简要总结
Patients with moderate or severe CMV disease less than 21 days old who have a maternal donor who has a CMV response to the peptivators will be screened.
All patients will receive treatment with valganciclovir or ganciclovir. There is a safety run in with treatment with CMV CTLs in cohort 1 and if found to be safe, will proceed to cohort 2 for randomization to receive antiviral therapy with or without CMV CTLs.
Funding source: FDA OOPD
详细描述
Given the vulnerability and poor outcomes of preterm neonates and neonates in general to viral infection, including the need for prolonged antiviral therapy for 6 or more months to achieve just modest improvements in sensorineural functions, CMV CTL therapy offers a promising alternative. CMV CTL treatment will build on the hosts innate immune capacity to create a more effective and permanent defense against collateral injury arising from CMV infections.
Patients who meet all inclusion/exclusion criteria with a maternal donor who meet all donor criteria will be enrolled onto study.
Cohort 1 is a safety run-in; the first 3 patients enrolled will be treated with anti-viral and CMV CTLs. The external DSMB will review the data from the first patient, and if there are no adverse events or dose-limiting toxicities observed, approve patient 2, and then 3, 28 days after the prior patients last CTL infusion. Assuming there are no adverse events in any of the first 3 patients, the study will proceed to Cohort 2.
Cohort 2 will be randomized 1:1 to either anti-viral treatment alone or anti-viral treatment plus CMV CTLs.
Patients who are randomized to receive CMV CTLs will get their first infusion on Day 0. If the patient fails to achieve a CR, they may receive one infusion every 2 weeks up to 5 maximum CMV CTL infusions as long as there are no DLTs or AEs observed
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
- None
入排标准
- 年龄范围
- 0 Days 至 21 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: ≤ 21 days of life
- •Birth Weight: ≥ 2500 gms
- •Gestational age: ≥ 34 weeks of age
- •Diagnosis of CMV viremia, viruria, and/or infection:Either one or more:
- •Elevated CMV by RT-PCR in urine, saliva, CSF, or plasma; and/or Positive urine culture for CMV
- •Moderate or Severe CMV Disease
- •Any one or more of the following attributable to congenital CMV infection:
- •Thrombocytopenia (≤ 50,000 mm3)
- •Multiple petechiae
- •Hepatomegaly
- •Splenomegaly
- •Intrauterine growth retardation
- •Increased transaminases
- •Increased bilirubin
- •Microcephaly
- •Ventriculomegaly
- •Intracerebral calcifications
- •Periventricular echogenicity
- •Cortical or cerebral malformation
- •Chorioretinitis
- •Severe neonatal hearing loss
- •CMV DNA by PCR in CNS
- •Increased WBC for age in CNS
- •Minimal Organ Criteria Hematological: ANC ≥ 750/mm3, HgB ≥ 8gm/dl, Platelets ≥ 20,000/kmm3 Renal: Serum creatinine ≤ 1.0 mg/dl Hepatic: ALT/SGOT ≤3x upper normal limits
- •Donor Availability: Maternal donor available with a T-cell response CMV MACS® PepTivators. the donor is considered suitable if the percentage of IFN-gamma+ T cells is > 0.01% after stimulation with PepTivators.
- •Exclusion Criteria -
- •Patient receiving steroids (> 0.5 mg/kg prednisone equivalent) on the same day of CMV CTL infusion. Antenatal steroids for lung maturation will have been cleared prior to CMV diagnosis.
- •Concomitant enrollment in another experimental clinical trial investigating the treatment of neonatal CMV viremia and/or infection.
- •Any medical condition that could compromise participation in the study according to the investigator's assessment.
- •Known history of HIV infection in the mother.
- •Patient's legally authorized representative unwilling or unable to comply with the protocol or unable to give informed consent.
排除标准
- 未提供
研究组 & 干预措施
Cohort 2 Antiviral medication + CMV CTLs
Patients will receive both anti-viral medication and CMV CTLs
干预措施: Anti-viral Therapy (Drug)
Cohort 1 Safety Run-in
The first 3 patients enrolled will receive both anti-viral medication and CMV CTLs, and treatment will be staggered every 28 days from the last dose of CMV CTLs from the prior patient.
干预措施: CMV Cytotoxic T-Lymphocytes (Biological)
Cohort 1 Safety Run-in
The first 3 patients enrolled will receive both anti-viral medication and CMV CTLs, and treatment will be staggered every 28 days from the last dose of CMV CTLs from the prior patient.
干预措施: Anti-viral Therapy (Drug)
Cohort 2 Antiviral medication + CMV CTLs
Patients will receive both anti-viral medication and CMV CTLs
干预措施: CMV Cytotoxic T-Lymphocytes (Biological)
Cohort 2 Antiviral medication only
Patients will only receive anti-viral therapy
干预措施: Anti-viral Therapy (Drug)
结局指标
主要结局
To determine the safety of giving CMV CTLs combined with anti-viral therapy in neonates with CMV
时间窗: 12 weeks
the incidence and severity of Grade I-IV acute GVHD within 8 weeks that is probably or directly related to CMV-CTL infusion after last CMV CTL infusion will be evaluated to determine the safety profile of CMV CTLs in neonates
To determine response rates to treatment with CMV CTLS and anti-viral medication
时间窗: 12 weeks
response rates will be measured by monitoring CMV PCR levels. A complete response to CMV-CTLs will be those with undetectable viral load by qRT-PCR
次要结局
未报告次要终点
研究者
Mitchell Cairo
Principal Investigator
New York Medical College