Pilot Study of Haploidentical or Matched Donor Virus-Specific T-cells (Cytomegalovirus (CMV) or Adenovirus (AdV)) to Treat CMV or AdV Reactivation or Disease in Patients After Solid Organ or Hematopoietic Stem Cell Transplantation (HCT)
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Feasibility defined as identifying a suitable donor within 4 weeks and meeting minimum T cell doses in the final product
研究概览
简要总结
This trial studies the side effects and how well allogeneic cytomegalovirus-specific cytotoxic T lymphocytes (donor cytomegalovirus [CMV] specific cytotoxic T-lymphocytes [CTLs]) or allogeneic adenovirus-specific cytotoxic T lymphocytes (donor adenovirus-specific [AdV] specific CTLs) work in treating CMV or AdV reactivation or infection in participants who have undergone stem cell transplant or solid organ transplant. White blood cells from donors may be able to kill cancer cells in patients with cytomegalovirus or adenovirus that has come back after a stem cell or solid organ transplant.
详细描述
PRIMARY OBJECTIVE I. Assess the safety and feasibility of administering virus specific-CTLs from haploidentical donors in transplant patients both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) with CMV/AdV infection despite standard therapy.
OUTLINE:Patients are assigned to 1 of 2 Cohorts.
COHORT A: Patients receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes intravenously (IV). Patients undergo blood, urine, saliva, cerebrospinal fluid (CSF), and bronchoalveolar fluid sample collection on the trial.
COHORT B: Patients receive allogeneic adenovirus-specific cytotoxic T Lymphocytes IV. Patients undergo blood, urine, saliva, CSF, and bronchoalveolar fluid sample collection on the trial.
After completion of study treatment, participants are followed up at 1 year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients must have solid organ transplant or have received allogeneic hematopoietic stem cell transplant.
- •• Cohort A (CMV): Must have documented CMV disease or reactivation, as by:
- •Viremia as detected by quantitative polymerase chain reaction (PCR) (> 500 IU/ml) in the peripheral blood requiring treatment OR
- •High risk for antiviral failure due to history of recurrent CMV reactivations or evidence of antiviral drug resistance, OR
- •Unable to tolerate antiviral drugs due to renal toxicity, bone marrow suppression, transfusion dependent anemia and thrombocytopenia or neutropenia requiring growth factor support or other related organ injury
- •Cohort B (AdV): Must have documented AdV infection or reactivation, as by:
- •Symptomatic subject with any detectable viral load in blood, OR
- •Symptomatic subject with qualitative AdV detection in compartment of current symptomatology, including stool, urine, and/or other specimens (bronchoalveolar lavage (BAL), nasal swab, CSF, etc.), irrespective of blood viral load, OR
- •New, persistent, and/or worsening AdV-related symptoms, signs, and/or markers of end organ compromise while receiving antiviral therapy (ie cidofovir), OR
- •Asymptomatic with a viral load > 1000 copies/ml in peripheral blood, OR
- •Unable to tolerate antiviral treatment due to renal toxicity, bone marrow suppression, transfusion dependent anemia and thrombocytopenia or neutropenia requiring growth factor support or other related organ injury
- •Karnofsky (age > 16 years) or Lansky performance score > 70 (age < 16)
- •Available seropositive haploidentical or matched donor who is without evidence of infection that would otherwise preclude donation
- •Negative pregnancy test in female patients if applicable (childbearing potential, has not received a full-intensity conditioning regimen
- •Written informed consent and/or signed assent line from patient, parent or guardian
- •Human leukocyte antigen (HLA)-haploidentical or full-match to the patient as determined by institutional standards
- •Cohort A: CMV seropositive, defined as detection of serum CMV immunoglobulin G (IgG)
- •Cohort B: AdV seropositive, defined as detection of serum AdV IgG
- •Age 18 or over
- •Meet donor eligibility or suitability according to institutional standards. If the donor is deemed ineligible according to Foundation for the Accreditation of Cellular Therapy (FACT) standards, but is suitable for donation per institutional standards, the donor will be eligible for the protocol
排除标准
- •Receipt of anti-thymocyte globulin (ATG), alemtuzumab, or other T-cell depleting agents within 21 days of screening for enrollment.
- •Receipt of > 0.5mg/kg/day of prednisone or steroid equivalent at the time of enrollment. Stable GVHD is permitted as long as patients are on stable dose steroids of less than or equal to 0.5 mg/kg/day of prednisone or steroid equivalent.
- •Evidence of uncontrolled infection as follows:
- •Bacterial infections - patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment.
- •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 with hemodynamic instability attributable to bacterial sepsis or new symptoms, worsening physical signs or radiographic findings attributable to concomitant bacterial or fungal infection are excluded. Patients who require ventilator support for CMV pneumonitis are not excluded. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- •Receipt of donor lymphocyte infusion (DLI) within 28 days.
- •Patients with active acute graft versus host disease (GvHD) grades II-IV requiring > 0.5 mg/kg/day of prednisone or steroid equivalent or T-cell depleting immunosuppression.
- •Acute graft rejection in solid organ transplantation requiring augmented immunosuppression with T-cell depleting agents or steroids as mentioned above.
- •Active and uncontrolled relapse of malignancy.
研究组 & 干预措施
Treatment (CMV-specific CTLs)
Participants receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes IV. Participants with persistent infection are eligible for second infusion after 28 days.
干预措施: Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes (Biological)
Treatment (AdV-specific CTLs)
Patients receive allogeneic adenovirus-specific cytotoxic T Lymphocytes IV. Participants with persistent infection are eligible for second infusion after 28 days.
干预措施: Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes (Biological)
结局指标
主要结局
Feasibility defined as identifying a suitable donor within 4 weeks and meeting minimum T cell doses in the final product
时间窗: Up to 1 year
Incidence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0
时间窗: Up to 30 days post infusion
Measured as the proportion of patients with acute (a) graft versus host disease (GvHD) grades III-IV or graft rejection/failure within 30 days of the last dose of cytotoxic T-lymphocytes (CTLs) or grades 3-5 infusion-related adverse events within 7 days of the last does of CTLs or grades 4-5 non-hematological adverse events within 30 days of the last dose of CTLs and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities. Will be calculated by dividing by all evaluable patients and the corresponding 95% confidence intervals will be calculated.
次要结局
- Antiviral activity defined as response to viral load(At day 28)
- Effects of cytomegalovirus (CMV) specific-CTL on viral loads assessed by weekly reverse transcriptase-polymerase chain reaction(Up to 1 year)
- Systemic infections(Within 6 months of CTL infusion)
- Secondary graft failure(30 days post-CTL infusion)
- Persistence of infused CTLs as measured by T cell gene rearrangement and effects on clinical signs of viral infection(Up to 1 year)
- Overall survival(From last CTL infusion till death, assessed at 6 and 12 months)
- Risk for chronic GVHD(At 6 and 12 months post CTL infusion)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0".(Up to 1 year)
- Viral reactivations(Up to 6 months)
- Clinical response to CTL infusions(At 6 weeks and 3 months)
研究者
Sumithira Vasu
Principal Investigator
Ohio State University Comprehensive Cancer Center