A Multi-center, Prospective Study of Clinical Outcome and Immune Reconstruction in G-CSF/ATG and PT-Cy Based Haploidentical Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Percent of participants with disease relapse
研究概览
简要总结
The goal of this observational study is to compare the incidence of relapse in G-CSF/ATG based and PT-Cy based haploidentical transplantation] in [patients aged 18 to 55 years with a diagnosis of hematological malignancies who unmanipulated haplo-HSCT with myeloablative conditioning]. The main question it aims to answer are:
Primary objective: To compare the incidence of relapse in G-CSF/ATG based and PT-Cy based haploidentical transplantation and illustrate the possible immune mechanism.
Secondary objectives: To compare CMV infection, GVHD and survival outcomes, and to observe the dynamic immune reconstitution of G-CSF/ATG based or PT-Cy based model.
Exploratory objectives: To compare the long-term quality of life among recipients who receive G-CSF/ATG based or PT-Cy based protocol.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects diagnosed as acute leukemia with transplant indications in ≤ CR2;
- •Lack of available, HLA-identical, related sibling or unrelated donor;
- •Female or male, age: 18-55 years old;
- •ECOG performance status 0-2;
- •Adequate organ function as defined by the following criteria:
- •Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤2.5× upper limit of normal (ULN), or AST and ALT ≤5× ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin≤1.5× ULN Serum creatinine≤2.5× ULN
- •Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment;
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
排除标准
- •Uncontrollable active infection;
- •Severe organic impairment: hepatic and renal impairment;
- •Any of the following within 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, congestive heart failure, or cerebrovascular accident including transient ischemic attack;
- •Pregnancy or breastfeeding;
- •Psychiatric disorders;
- •Don't sign the informed consent;
- •Prior/concurrent clinical study experience;
- •Other conditions:
- •Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
- •Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6)
- •Any specific situation during study implementation/course that may rise ethics considerations
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
研究组 & 干预措施
G-CSF/ATG group
Patients in the G-CSF/ATG group received a modified Bu/Cy plus ATG conditioning regimen as follows: cytarabine (4/g m2 per day IV.) on days -10 to -9; Bu (3.2 mg/kg per day IV.) on days -8 to -6; Cy (1.8 g/m2 per day IV.) on days -5 to -4; methyl chloride hexamethylene urea nitrate (Me-CCNU) (250 mg/m2 per day orally) once on day -3; and ATG (2.5 mg/kg per day IV; rabbit, Sang Stat, Lyon, France) on days -5 to -2.
干预措施: ATG (Drug)
PT-Cy group
Patients in PT-Cy group received a Bu/Flu/Cy-based conditioning regimen as follows: Flu (40 mg/m2 or 1 mg/kg IV) on days -8 to -4; Bu (3.2 mg kg/ d-1 IV) on days -7 to -4; Cy (14.5-40 mg/kg IV) on days -3 to -2;±cytarabine (3 g/m2/d IV) on days -9 to -8; and ± IDA (15 mg/m2/d IV) on days -9 to -8. The addition of IDA and/or cytarabine depended on the performance status of the patients and whether the patients were in relapse status. High-dose PTCy (50 mg/kg/d IV) was administered on days +3 and +4.
干预措施: Post-transplantation cyclophosphamide (Drug)
结局指标
主要结局
Percent of participants with disease relapse
时间窗: 1 year
The cumulative incidence of relapse of the primary disease.
次要结局
- Transplantation-related mortality(1 year)
- Incidence of CMV disease(6 months)
- Cumulative incidences of aGVHD(100 days)
- Cumulative incidences of cGVHD(1 year)
- Percent of participants with overall survival(1 year)
- Dynamic immune reconstitution(1 year)
- Neutrophil engraftment(1 month)
- Platelet engraftment(1 month)
研究者
Xiao-Jun Huang
Prof.
Peking University People's Hospital