A Pilot Study in the Treatment of BK Virus Infection With Cytotoxic T Cells in Immunocompromised Transplant Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Number of patients with undetectable BK viral load
研究概览
简要总结
This is a pilot study using cytotoxic T lymphocytes (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Gamma-capture system will be effective in decreasing specific viral load in patients with BK virus viremia and BK virus-associated symptoms post-allogeneic hematopoietic stem cell transplantation (HSCT), renal transplantation, and chemotherapy.
详细描述
This open-label, single-arm clinical trial will assess the safety and efficacy of BK virus-specific CTLs isolated from whole blood or leukapheresis products. The BK virus -specific CTLs will be generated automatically by the CliniMACS® Prodigy using the CliniMACS Cytokine Capture System (IFNgamma) after incubation with MACS GMP PepTivator® Peptide Pools of BKV VP1 and BKV LT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 5 Weeks 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient Eligibility
- •Patients with symptoms of cystitis and elevated BK virus DNA by screening PCR as above (section 4) post allogeneic HSCT, post chemotherapy
- •Symptoms of cystitis may include: hematuria (microscopic or gross), pain with urination, frequency, bladder spasms.
- •Patient may be otherwise treated for cystitis as per local institutional standards. Such treatments may include hydration, antiviral medications, or surgical intervention as deemed appropriate by treating physician.
- •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 yrs)
- •Age: 0.1 to 25 years
- •Females of childbearing potential with a negative urine pregnancy test.
- •Donor Eligibility
- •Related donor available with a T-cell response to the BK-virus MACS® PepTivator® antigen(s).
- •Original allogeneic donor if available, IgG positive for BKV or confirmatory testing to respond to BKV MACS Peptivator®.
- •Third Party Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with a T-cell response to the BK MACS® PepTivator.
- •Allogeneic donor disease screening is complete similar to hematopoietic stem cell donors (Appendix 1).
- •Obtained informed consents by donor or donor legally authorized representative prior to donor collection.
排除标准
- •Patient exclusion criteria:
- •A patient meeting any of the following criteria is not eligible for the present study:
- •Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of BK Virus CTL infusion
- •Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of BK Virus CTL infusion or within 3 days of planned infusion.
- •Thymoglobulin (ATG), campath or T cell immunosuppressive monoclonal antibodies within 30 days
- •Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30%
- •Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory BK virus infection.
- •Any medical condition which could compromise participation in the study according to the investigator's assessment
- •Known HIV infection
- •Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment.
- •Known hypersensitivity to iron dextran
- •Patients unwilling or unable to comply with the protocol or unable to give informed consent.
- •Known human anti-mouse antibodies
研究组 & 干预措施
BK cystitis and/or nephropathy
All patients with symptoms that are consistent with BK cystitis and/or nephropathy (frequency, dysuria, hematuria, elevated creatinine) will have serum quantitative DNA PCR for BK virus level measured in log copies per mL (results also expressed in copies per milliliter), performed in the Children's Hospital of Philadelphia Infectious Disease Diagnostics Laboratory
干预措施: BK-virus specific CTLs (Biological)
结局指标
主要结局
Number of patients with undetectable BK viral load
时间窗: 12 weeks after first BK-CTL infusion
Number of patients with undetectable BK viral load as measured by qPCR
Number of participants with Grade III-IV acute GVHD
时间窗: Up to 8 weeks after last BK-CTL infusion
Number of participants with Grade III-IV acute GVHD as assessed by CTCAE v4.0
次要结局
未报告次要终点
研究者
Caitlin Elgarten
Attending Physician, Assistant Professor, Perelman School of Medicine at the University of Pennsylvania
Children's Hospital of Philadelphia