Phase II Study Assessing the Effect of BK Specific CTL Lines Generated by Ex Vivo Expansion in Patients With BK Virus Infection and JC Virus Infection
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase II trial studies how well donor cytotoxic T lymphocytes work in treating patients with malignancies with BK and/or JC virus. Cytotoxic T lymphocytes are made from donated blood cells that are grown in the laboratory and are designed to kill viruses that can cause infections in transplant patients and may be an effective treatment in patients with malignancies with BK and/or JC virus.
详细描述
PRIMARY OBJECTIVE:
I. To assess the efficacy, feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched BK specific cytotoxic T lymphocyte (CTL) lines (BK-CTLs) generated by ex vivo expansion to mediate antiviral activity in patients with any type of malignancies, and/or HIV/AIDs, and/or history of solid organ transplant with BK and JC infections.,
SECONDARY OBJECTIVE:
I. To assess the persistence of the administered BK-CTLs generated by ex vivo expansion in immunocompromised patients, patients with any type of malignancies, or HIV/AIDs, and/or history of solid organ transplant with BK and JC infections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 2 years.
- •English and non-English speaking patients are eligible.
- •Immunocompromised patients including but not limited to those with any type of malignancy, HIV/AIDS, or history of solid organ transplant
- •Non-immunocompromised patients with PML/JC virus encephalitis
- •Microscopic or greater hematuria urine or blood PCR positive for BK virus
- •Biopsy proven BK nephritis and urine or blood PCR positive for BK virus disease and/or polyomavirus.
- •Definite or probable PML/JC viral encephalitis (see Appendix C)
- •JC end-organ disease
- •Receiving > 6 mg / day of prednisone or equivalent at the time of enrollment.
- •Patients with BK virus hemorrhagic cystitis, who are receiving treatment with cidofovir, leflunomide, or other antiviral therapy with no response, will be eligible for CTL infusion.
- •Patients with JCV encephalitis / PML may be receiving pembrolizumab.
- •Written informed consent and/or signed assent from patient, parent or guardian.
- •Patients with cognitive impairments are eligible.
- •A negative pregnancy test in female patients of childbearing potential. Childbearing potential is defined as pre-menopausal, post-menopausal for < 1 year, and not having undergone surgical sterilization.
- •Women of childbearing potential must be willing to use an effective contraceptive measure while on study.
- •Patients enrolled on this study may be enrolled on other IND studies at the discretion of the PI.
- •Patients with bacterial infections must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment.
- •Patients with fungal infections patients must be receiving definitive systemic anti fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
- •Patients may be re-enrolled in the protocol if the BK or JC virus infection recurs, so long as they meet all the other eligibility criteria at the time of re-enrollment.
排除标准
- •Patients receiving > 6 mg / day of prednisone or equivalent at time of
- •Patients who have received ATG within 14 days of enrollment
- •Patients who have received donor lymphocyte infusion (DLI) within 28 days of enrollment.
- •Patients who have received alemtuzumab within 28 days of enrollment.
- •Patients with other uncontrolled infections (including HIV/AIDS). Uncontrolled infection is defined as the presence of hemodynamic instability attributable to sepsis, or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as uncontrolled infection.
- •Patients with active acute GVHD grades II-IV.
研究组 & 干预措施
Treatment (BK-specific cytotoxic T lymphocytes)
Patients receive allogeneic BK-specific cytotoxic T-lymphocytes IV over 30 minutes. Patients achieving partial response, stable disease, or progressive disease are eligible for 19 additional infusions of CTL occurring at least 2 weeks after the previous CTL infusion if they meet the eligibility criteria for subsequent therapy.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (BK-specific cytotoxic T lymphocytes)
Patients receive allogeneic BK-specific cytotoxic T-lymphocytes IV over 30 minutes. Patients achieving partial response, stable disease, or progressive disease are eligible for 19 additional infusions of CTL occurring at least 2 weeks after the previous CTL infusion if they meet the eligibility criteria for subsequent therapy.
干预措施: Allogeneic BK-specific Cytotoxic T-lymphocytes (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to day 100
Will be continuously monitored.
Incidence of acute graft-versus-host disease (GVHD)
时间窗: Within 28 days of the last dose of cytotoxic T lymphocytes (CTLs)
The method of Thall et al will be used to monitor the probabilities of grade 3 or 4 GVHD.
Response, defined as response (R) = (best response [R1] or second best response [R2])
时间窗: Up to 56 days
The method of Thall et al will be used to monitor the probabilities of response.
次要结局
- Glomerular filtration rate(Up to 12 months)
- Overall survival(Up to 12 months)