An Open-Label Prospective Randomized Trial of Family Donor-Derived ADV or CMV CTLs Plus Standard of Care (SOC) vs SOC Alone in Children, Adolescents and Young Adults Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) With Refractory ADV or CMV Infection/Viremia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 2
- 主要终点
- Viral PCR to determine resolution of disease
研究概览
简要总结
Patients with refractory ADV or CMV infection post allogeneic stem cell transplant will be randomized to either Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) plus standard of care (SOC) vs SOC alone.
详细描述
We hypothesize that Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) manufactured by direct selection utilizing the CliniMACS Prodigy® and Cytokine Capture System® plus standard of care (SOC) vs SOC alone in children, adolescents and young adults (CAYA) following allogeneic hematopoietic stem cell transplantation (HSCT) with medically refractory viral infection/viremia and/or intolerant or resistant to anti-viral antibiotic therapy will be associated with a significantly improved probability of Day +100 (time of onset on study) viral progression free survival (VPFS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient Eligibility Cohort 1 (ADV) -Patients with ADV viremia (Cohort 1) post AlloHSCT with one or more of the following: Increasing or persistent ADV RT-PCR DNA (> 1000 ADV PCR copies) after 7 days of appropriate anti-viral therapy AND/OR Medical intolerance to anti-viral therapies including one or more of the following: > grade 2 renal insufficiency secondary to cidofovir and/or other > grade 2 toxicities secondary to cidofovir AND/OR Known resistance to cidofovir
- •Patient Eligibility (Cohort 2) (CMV)
- •Patients with CMV viremia with one or more of the following: Increasing or persistent CMV RT-PCR DNA (>1000 copies) after 7 days of appropriate anti-viral therapy AND/OR Medical intolerance to anti-CMV antibiotic therapies: ANC < 500/mm3 secondary to ganciclovir AND/OR > grade 2 renal toxicity secondary to either foscarnet or cidofovir AND/OR Known resistance to ganciclovir and/or foscarnet
- •Consent: written informed consent given (by patient or legal representative) prior to any study related procedures
- •Performance Status >30% (Lansky < 16 yrs and Karnofsky > 16 years (BOTH COHORTS)
- •Age: 0.01 to 30.00 years (BOTH COHORTS)
- •Females of childbearing potential with a negative urine pregnancy test at study entry only (BOTH COHORTS)
- •Family related donor (> 3 HLA match) that screens positive for ADV5 MACS Peptivator (Cohort 1) or PP65CMV MACS Peptivator (Cohort 2)
- •Donor Eligibility
- •Related donor available with a T-cell response to the ADV MACS PepTivators (Cohort 1) or CMV MACS PepTivator (Cohort 2). As defined in Appendix II, B, 8.2, the donor is considered suitable if the percentage of IFN+ T-cells is >0.01% after stimulation with ADV PepTivators (Cohort 1) or CMV PepTivators (Cohort 2).
- •Third-party related allogeneic donor: If original donor is not available or does not have a T-cell response to ADV MCAS PepTivator (Cohort 1) or CMV PepTivator (Cohort 2), third party allogeneic donor (family donor > 3 HLA A, B, DR match to recipient) with a T-cell response at least to the ADV MCAS PepTivator (Cohort 1) or CMV PepTivator (Cohort 2) AND
- •Allogeneic donor disease screening is complete similar to hematopoietic stem cell donors (Appendix 1) AND
- •Obtained informed consents by donor or donor legally authorized representative prior to donor collection
排除标准
- •(Both Cohorts)
- •Patient with acute GVHD > grade 2 or moderate or extensive chronic GVHD at the time of CTL infusion.
- •Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of CTL infusion.
- •Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion.
- •Patient with poor performance status determined by Karnofksy (patients > 16 yrs) or Lansky (patients < 16 years) score < 30%.
- •Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory ADV or CMV infections.
- •Any known medical condition which cold compromise participation in the study according to investigators assessment.
- •Known AIDS or uncontrolled HIV infection
- •Known hypersensitivity to iron dextran
- •Encephalitis and/or retinitis
研究组 & 干预措施
Standard of Care Medication
Patients will receive standard of care antiviral therapy for CMV or ADV at the discretion of the physician.
干预措施: Standard of Care Antiviral medications (Drug)
Standard of Care Medication plus Cytotoxic T-Lymphocytes (CTLs)
Patients will be randomized to receiving standard of care antiviral therapy plus family matched donor derived CTLs.
干预措施: Standard of Care Antiviral medications (Drug)
Standard of Care Medication plus Cytotoxic T-Lymphocytes (CTLs)
Patients will be randomized to receiving standard of care antiviral therapy plus family matched donor derived CTLs.
干预措施: Viral CTLs (Biological)
结局指标
主要结局
Viral PCR to determine resolution of disease
时间窗: Day 100
Patients will be monitored weekly by peripheral blood qtPCR values to monitor viral levels for resolution confirmation.
次要结局
未报告次要终点