A Phase IB-II Study Of High-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus for the Prevention of Graft-Versus-Host Disease (GvHD) Following Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Grade II-IV Acute GvHD by Day +120
研究概览
简要总结
This is a single arm, open label, optimal 2-stage Simon design phase Ib-II clinical trial. Adult patients with hematological malignancies undergoing allogeneic HSCT from first- or second-degree haploidentical donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive non-myeloablative, reduced-intensity or myeloablative conditioning regimen followed by peripheral blood hematopoietic stem cells. Patients will receive cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Age ≥ 18 years
- •Karnofsky score ≥ 70%
- •No evidence of progressive bacterial, viral, or fungal infection
- •Creatinine clearance > 50 mL/min/1.72m2
- •Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for diagnosed Gilbert's syndrome)
- •Alkaline phosphatase ≤ 250 IU/L
- •Left Ventricular Ejection Fraction (LVEF) > 45%
- •Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%
- •Negative HIV serology
- •Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG) for women of childbearing age and potential.
排除标准
- •Donors are excluded in case of donor-specific HLA antibodies or positive cross-match.
- •Pregnant or nursing females or women of child bearing age or potential, who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from the first dose of conditioning regimen through day +
- •A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 months in a row.
- •Male subjects who refuse to practice effective barrier contraception during the entire study treatment period and through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post-vasectomy).
- •Inability to provide informed consent.
- •Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix E), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- •Known allergies to any of the components of the investigational treatment regimen.
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
研究组 & 干预措施
HSCT Patients
Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.
干预措施: Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention (Drug)
结局指标
主要结局
Percentage of Participants With Grade II-IV Acute GvHD by Day +120
时间窗: 120 days
The first day of grade II-IV acute GvHD will be used to calculate the cumulative incidence. The cumulative incidence will be defined as the percentage of participants with grade II-IV acute GvHD. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. Overall Grades of Acute GvHD: 0 = none; 1. = mild; 2. = moderate; 3. = severe; 4. = life threatening
次要结局
- Cumulative Incidence of Chronic GvHD(Day 365)
- Cumulative Incidence of Primary Graft Failure(Day 45)
- Cumulative Incidence of Poor Graft Function(Day 28)
- Incidence of Secondary Graft Failure(Day 730)
- Number of Treatment-Related Deaths(Day 730)
- Relapse Rate(Day 730)
- GvHD and Relapse-Free Survival (GRFS)(Day 730)
- Overall Survival(Day 730)