Rabies Vaccination to Assess Vaccine Responsiveness After B Cell Targeted CAR-T Cell Therapies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Proportion of participants with positive vaccine response
研究概览
简要总结
This phase I trial will use the inactivated rabies virus vaccine to assess immune function in patients who previously underwent B cell targeted chimeric antigen receptor-modified T cell immunotherapy (CARTx). A cohort of healthy volunteers will also be enrolled as a comparator group. CARTx is a new treatment for patients with B-cell malignancies (cancer of the B-cells), and the long-term effects of CARTx on immune function are not yet well understood. Learning more about vaccine responsiveness in patients who previously underwent CARTx may help doctors better understand immune function. The findings will guide evidence-based strategies for infection prevention to improve outcomes in this rapidly growing population of high-risk individuals.
详细描述
STUDY DESIGN:
This study will be a prospective, open-label clinical trial of primary and secondary vaccination with the inactivated rabies vaccine in patients treated with CARTx for B cell malignancies and healthy individuals. The target enrollment for this trial is 43 CARTx recipients and 10 healthy controls. The study is open to anyone regardless of gender or ethnicity.
OUTLINE:
BOLUS COHORT: Patients receive the inactivated rabies vaccine intramuscularly (IM) on day 1 and 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization. This will include up to 31 participants.
FRACTIONAL DOSE COHORT: Patients receive the inactivated rabies vaccine fractionated primary dose IM on days 1, 3, 7, 10, 14, and 17 and the second dose 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization. This will include up to 12 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •CARTx RECIPIENTS: Patients must be capable of understanding and providing a written informed consent
- •CARTx RECIPIENTS: Patients must be 18 years of age or older, of any gender, race or ethnicity
- •CARTx RECIPIENTS: Patients must have had relapse-free survival for >= 6 months after receiving CARTx for B-cell malignancies
- •CARTx RECIPIENTS: Platelet count > 30,000 / mm^3
- •HEALTHY CONTROLS: Patients must be capable of understanding and providing a written informed consent
- •HEALTHY CONTROLS: Patients must be 18 years of age or older, of any gender, race or ethnicity
排除标准
- •CARTx RECIPIENTS: Patients who have received a hematopoietic cell transplant after CARTx
- •CARTx RECIPIENTS: Previously received 1 or more rabies vaccines prior to the first vaccine visit
- •CARTx RECIPIENTS: Patients who have received lymphodepleting therapies after CARTx and within the past 6 months
- •CARTx RECIPIENTS: Patients with signs or symptoms of active infection
- •CARTx RECIPIENTS: Patients who are pregnant or breastfeeding
- •CARTx RECIPIENTS: Patients with previous known allergies to any component of the vaccine
- •CARTx RECIPIENTS: Patients who have previously experienced a reaction to any vaccine that required medical attention
- •CARTx RECIPIENTS: Study participants who report a severe adverse event following the first rabies vaccine will not be eligible for a second dose
- •CARTx RECIPIENTS: Receiving corticosteroids > 0.5 mg/kg/day prednisone equivalence in the 7 days prior to first or second vaccination
- •HEALTHY CONTROLS: Previously received 1 or more rabies vaccines
- •HEALTHY CONTROLS: Chronic illness
- •HEALTHY CONTROLS: Signs or symptoms of active infection
- •HEALTHY CONTROLS: Pregnant or breastfeeding
- •HEALTHY CONTROLS: Patients with previous known allergies to any component of the vaccine
- •HEALTHY CONTROLS: Previous reaction to a vaccine that required medical attention
研究组 & 干预措施
Experimental (anti-rabies vaccine, collection of blood)
BOLUS COHORT: Patients receive the inactivated rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization.
FRACTIONAL DOSE COHORT: Patients receive the inactivated rabies vaccine fractionated primary dose IM on days 1, 3, 7, 10, 14, and 17 and the second dose 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization.
干预措施: Wistar Rabies Virus Strain PM-1503-3M Vaccine (Biological)
Experimental (anti-rabies vaccine, collection of blood)
BOLUS COHORT: Patients receive the inactivated rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization.
FRACTIONAL DOSE COHORT: Patients receive the inactivated rabies vaccine fractionated primary dose IM on days 1, 3, 7, 10, 14, and 17 and the second dose 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization.
干预措施: Biospecimen Collection (Procedure)
Control (anti-rabies vaccine, collection of blood)
Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.
干预措施: Wistar Rabies Virus Strain PM-1503-3M Vaccine (Biological)
Control (anti-rabies vaccine, collection of blood)
Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
Proportion of participants with positive vaccine response
时间窗: 4 weeks after the secondary vaccination
This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at week 4 post-secondary immunization. This RVNA titer is considered to be evidence of an adequate immune response by the World Health Organization. Will estimate with 95% confidence intervals.
次要结局
- Proportion of participants with sustained vaccine response(6 months after the primary vaccination)
- Longitudinal rabies virus neutralizing antibody (RVNA) titers(From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.)
- Longitudinal rabies virus binding IgM antibody titers(From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.)
- Longitudinal rabies virus binding IgG antibody titers(From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.)