Fecal Microbiota Transplantation in Patients Undergoing Chimeric Antigen Receptor T-cell Therapy and Allogeneic Stem Cell Transplant: A Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To evaluate the feasibility of fecal microbiota transplantation (FMT) in patients undergoing CAR-T or allogeneic stem cell transplantation.
研究概览
简要总结
This is a single site pilot trial will evaluate the feasibility and safety of fecal microbiota transplantation (FMT) in patients with B-cell lymphoma who are undergoing CAR-T or in patients with moderate to high-risk acute myeloid leukemia or myelodysplastic syndrome who are undergoing allogeneic stem cell transplantation.
详细描述
This is a single centre, non-randomized, single-arm interventional pilot study examining fecal microbiota transplantation in patients undergoing CAR-T or allogeneic stem cell transplantation (alloSCT). 20 eligible patients will be enrolled in this study 10 patients with B-cell lymphoma undergoing CAR-T and 10 patients with AML/MDS undergoing alloSCT. FMT series occurring prior to cellular therapy and 30 days after cellular therapy treatment. Standard of care blood tests including HIV, Hepatitis B and C testing, pregnancy test and physical exam will be done during the study. Blood, urine, rectal swab, stool sample will be collected for correlative studies. Patients will be asked to complete a questionnaire questionnaire on perceptions and acceptability of FMT. The total study duration will be approximately 2.5 years, including 2 years of recruitment, minimum 1 series of FMT treatments and a minimum 6 months of follow-up.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ≥ 18 years of age
- •Diagnosis of the following:
- •Indolent or aggressive B-cell lymphoma eligible for standard or care CAR-T therapy (Cohort A), or
- •Patients with AML or high risk MDS with indication to undergo reduced-intensity conditioning alloSCT, with an available matched related, unrelated, or haploidentical donor (Cohort B)
- •Adequate marrow function defined by:
- •Hemoglobin >80 g/L without transfusion dependence within the last 7 days
- •Platelet count >20 x 109/L without transfusion dependence within the last 7 days
- •Neutrophil count >1.0 x 109/L without growth factor support within the last 7 days
- •Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limits of normal (ULNs) value; serum total bilirubin < 1.5 x ULN (unless documented Gilbert's syndrome)
- •Adequate renal function as defined as creatinine clearance ≥ 30 mL/min directly measured with a 24-hour urine collection or calculated according to the modified formula of Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation
- •Life expectancy >6 months
- •Women of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and up to 6 months after the last dose of protocol therapy. Men who are sexually active must use highly effective methods of contraception during treatment and up to 6 months after the last dose of protocol therapy. Men require an agreement to remain abstinent (ie, refrain from heterosexual intercourse) or use a condom, and an agreement to refrain from donating sperm. Periodic abstinence and withdrawal are not acceptable methods of contraception. Fertility preservation options should be discussed. Examples of highly effective contraceptive methods include an agreement to remain abstinent (ie, refrain from heterosexual intercourse), bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
- •Willing and able to participate in all required evaluations and procedures in this study.
- •Ability to understand and the willingness to sign a written informed consent.
排除标准
- •For patients undergoing alloSCT (Cohort B): plan to undergo myeloablative conditioning
- •Use of investigational agents within the last 4 weeks before enrollment.
- •Active or uncontrolled infection
- •Autoimmune disorder currently being treated with disease-modifying therapy or with >10mg/day prednisone
- •Inflammatory bowel disease
- •History of intestinal perforation
- •Gastrointestinal surgical procedure within the past 4 weeks before enrollment
- •Pregnant or breast-feeding patients
- •HIV infection with detectable viral load or CD4 count <200
- •Serologic status reflecting active hepatitis B or C infection as follows:
- •Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA. (Note, patients with undetectable HBV DNA are permitted to enroll if they are on Hepatitis B suppressive therapy)
- •Patients with presence of hepatitis C virus (HCV) antibody and HCV RNA detectable
- •History of infection or known colonization with antibiotic resistant organism in the last two years before enrollment (including ESBL, MRSA, VISA, VRSA, VRE, CPE)
- •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in the study
研究组 & 干预措施
Allogenic stem cell transplant
Patients will receive Fecal microbiota transplantation and allogenic cell trnsplant
干预措施: Fecal Microbial Transplant Enema (Biological)
CAR-T cell transplant
Patients will receive Fecal microbiota transplantation and CAR-T cell infusion
干预措施: Fecal Microbial Transplant Enema (Biological)
结局指标
主要结局
To evaluate the feasibility of fecal microbiota transplantation (FMT) in patients undergoing CAR-T or allogeneic stem cell transplantation.
时间窗: 2.5 years
The study hypothesizes successful recruitment of at least 50% of approached patients, retain at least 80% of patients on the study, and successfully administer at least one FMT series to 80% of retained patients.
To evaluate the safety of fecal microbiota transplantation (FMT) in patients undergoing CAR-T or allogeneic stem cell transplantation.
时间窗: 2.5 years
The study hypothesizes that FMT will be safe in this population. Each cohort will be considered separately in considering the differing risks of CAR-T and alloSCT. The study hypothesizes that in each cohort there will be no greater than 10% incidence (N\< 1 of 10 participants in each cohort), of serious adverse events, or Grade \>3 adverse events of special interest (sepsis and/or bacteremia, ICU admission, bowel perforation, or death) within 48 hours of administration of FMT, which are judged to be possibly, probably or definitely related to FMT.
次要结局
未报告次要终点