Open-label, prospective, multi-center, single-arm, academic clinical trial of oral Valganciclovir (VGCV) as pre-emptive therapy for ‘low-risk’ cytomegalovirus reactivation following alloHCT in children
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- The primary endpoint is confirmed clearance of CMV viremia (assessed by PCR) three weeks after start of VGCV treatment.
研究概览
简要总结
Intravenous ganciclovir GCV, currently the recommended standard treatment for cytomegalovirus CMV disease in transplant recipients in India, requires hospitalization, often a central intravenous line, and thus is expensive and inconvenient for patients. A safe and effective oral therapy may significantly improve and simplify the management of posttransplant CMV disease. Oral VGCV showed comparable safety and was not inferior to intravenous GCV for treatment of CMV disease in organ transplant recipients and provided a simpler treatment strategy in a randomized, open-label, parallel-group, active drug-controlled, multi-center noninferiority trial at 42 centers including 326 patients. Adult solid organ transplant recipients with both virologic and clinical evidence of CMV disease, regardless of donor or recipient CMV serostatus were enrolled into this trial. Baseline viral loads were not different between groups. Side-effects and discontinuations of assigned treatment were comparable. The success rate at day 21 defined as a negative plasma polymerase chain reaction PCR, Roche Diagnostics, USA with a cut-off of 600 copies per mL for CMV was 45.1 percentage for VGCV and 48.4 percentage for GCV. Winston et al. studied the pharmacokinetics of VGCV and GCV in a cross-over design in adult patients after allogeneic stem cell transplantation with Graft-versus-Host Disease GVHD of the gastrointestinal tract and established noninferiority of VGCV. Data on pediatric patients after allogeneic HCT alloHCT are available from a phase II trial in which all patients first received GCV but some patients later on switched to the oral drug. Both treatments were equally effective. VGCV is not approved by European Medicines Agency EMA or U.S. Food and Drug Administration FDA for the pre-emptive treatment of CMV reactivations in pediatric patients following alloHCT but still is common practice in many experienced centers. Therefore, this trial aims at demonstrating safety and efficacy of VGCV for the pre-emptive treatment of pediatric patients with CMV reactivation after alloHCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 3.00 Year(s) 至 18.00 Year(s)（—）
- 性别
- All
入选标准
- •Signed written Informed Consent or Assent.
- •First CMV reactivation following alloHCT.
- •Two CMV reports with greater than 1,000 copies per milliliter or 1 CMV report with Greater than 10,000 copies per milliliter.
- •Males and females at an age between 3 and 18 years.
- •Minimum body weight of 10 kg.
- •Diagnosis of thalassemia, severe aplastic anemia, sickle cell disease or Fanconi’s anemia.
- •For women of child bearing potential: a negative pregnancy test.
排除标准
- •Life-threatening CMV infection defined by: DNAemia with greater than 100,000 copies per millilitre or Clinically suspected CMV pneumonitis Liver blood tests suggestive of CMV hepatitis such as Alanine aminotransferase greater than 3 times upper limit of norm and Aspartate aminotransferase or Alanine aminotransferase ratio less than 1 within one week prior to enrolment.
- •Watery diarrhea: greater than or equal to 3 stools per day and abdominal cramps as clinical signs suggestive of CMV enterocolitis within 48 hours prior to enrolment.
- •Acute gut GVHD organ grade two to four.
- •Neutrophil count less than 500 million cells per liter Patients with watery diarrhea greater than or equal to 3 stools per day and abdominal cramps, or bloody diarrhea for any reason within 48 hours prior to enrolment.
- •History of significant adverse reaction to GCV, VGCV, aciclovir or valacyclovir.
- •Clinically or molecularly proven GCV resistance.
- •Treatment with an investigational drug within the last 28 days.
- •Creatinine clearance less than 60 mL per minute per 1.73 meter square as calculated with the modified Schwartz formula.
- •Need for intensive care.
- •Inability to take oral drugs.
- •Simultaneous participation in another clinical trial.
结局指标
主要结局
The primary endpoint is confirmed clearance of CMV viremia (assessed by PCR) three weeks after start of VGCV treatment.
时间窗: 3 weeks
次要结局
- The following secondary endpoints will be addressed in all populations: Rate of neutropenia & thrombocytopenia, VGCV pharmacokinetics, CMV clearance & rate of recurrent CMV reactivation.(Efficacy of oral valganciclovir will be tested on day 5 or 6 after administration of medication. Rate of neutropenia at week 3. Thrombocytopenia will be checked at week 3. Rate of CMV recurrence at week 12 after trial start for each subject.)