Vaccination Against Human Papillomavirus (HPV) in Women and Men After Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 5
- 主要终点
- Primary outcome - GMT level against HPV 16
研究概览
简要总结
Patients who undergo allogeneic stem cell transplantation lose previously acquired immunity and are routinely revaccinated against many infectious diseases. For several reasons, these patients have a long-term immune deficiency due to the transplant itself (lack of immune reconstitution) and due to possible complications, primarily GvHD and its treatment. The risk of secondary malignancy in the long-term following an allogeneic bone marrow transplant is greatly increased, and secondary cancer cases account for a significant proportion of late deaths in both women and men after transplantation. Some of these secondary cancers are associated with HPV. The risk of cervical cancer has been reported to be 13 times increased compared to a healthy population.
Therefore in this trial, the aim is to study immune response (antigen-specific antibody response) after vaccination with 9-valent HPV vaccine (Gardasil 9®) in adult women and men (up to and including 45 years of age) who have undergone allogeneic stem cell transplantation. In this trial, the sponsor will compare "early" (start 9 months after tx) with "late" (start 15 months after tx) vaccination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient of AlloSCT from related or unrelated donor.
- •Adults (men and women) ≥18 years up to and including 45 years of age for vaccination.
- •Patients can be included regardless of prior HPV vaccination prior to transplantation
排除标准
- •Severe thrombocytopenia (under 50 x 10^9) not allowing intramuscular injection
- •Severe acute GvHD grade III-IV.
- •Extensive chronic GvHD requiring treatment with prednisone doses above 0.7 mg/kg/day plus at least two other systemic treatments against GvHD (for example ruxolitinib or photopheresis).
- •Prednisone doses above 1mg/kg/day at study start.
- •Treatment with rituximab 6 months before start of vaccination. Doses given later (unusual) do not require exclusion.
- •Treatment within 3 months before start of vaccination with iv or sc immunoglobulin.
- •Pregnancy, pregnancy desire or active pregnancy planning during time vaccine is given and up to three months after last vaccine dose.
- •Treatment with blood thinning medication contraindicating intramuscular injection
- •Allergy against Gardasil 9
研究组 & 干预措施
Late vaccination group
Subjects will receive Gardasil 9® as part of the late post-transplant vaccination, starting at 15 months after stem cell transplantation.
干预措施: Late post-transplant vaccination with Gardasil 9® (Biological)
Early vaccination group
Subjects will receive Gardasil 9® as part of the early post-transplant vaccination, starting at 9 months after stem cell transplantation.
干预措施: Early start post-transplant vaccination with Gardasil 9® (Biological)
结局指标
主要结局
Primary outcome - GMT level against HPV 16
时间窗: Early group: at month 16 posttransplant. Late group: at month 22 posttransplant.
Antibody level (GMT - geometric mean titer) against HPV 16 measured 1 months after the third vaccine dose, early vs late.
次要结局
- Secondary outcome 1 - GMT level against all 9 HPV-serotypes(Early group: at month 16 posttransplant. Late group: at month 22 posttransplant.)
- Secondary Outcome 5 - Proportion seropositive against 7/9 HPV-types(Early group: at month 16 and month 27 posttransplant. Late group: at month 22 and month 33 posttransplant.)
- Secondary Outcome 3 - Proportion seropositive/negative against 9 HPV-serotypes(Early group: at month 16 and month 27 posttransplant. Late group: at month 22 and month 33 posttransplant.)
- Secondary Outcome 2 - GMT level against all 9 HPV-serotypes(Early group: at month 27 posttransplant. Late group: at month 33 posttransplant.)
- Secondary Outcome 4 - Seroconversion against 9 HPV-serotypes(Early group: at month 16 posttransplant. Late group: at month 22 posttransplant.)