A Single-center, Prospective Trial of the Safety and Efficacy of UCMSC-Exo in Consolidation Chemotherapy-induced Myelosuppression in Patients With Acute Myeloid Leukemia After Achieving Complete Remission
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of the study is to explore the safety and efficacy of UCMSC-Exo in consolidation chemotherapy-induced myelosuppression in patients with acute myeloid leukemia after achieving complete remission.
详细描述
Despite the improved prognosis of patients with acute myeloid leukemia, almost all patients will experience severe myelosuppression induced by chemotherapy, leading to a series of complications such as infection due to neutropenia, bleeding due to thrombocytopenia and/or impaired major organ function such as cardiac function due to anemia, which are the main reasons for dose reduction, dose interruptions of chemotherapy and also treatment-related death. It is of significant clinical importance and an urgent need to promote early recovery of myelosuppression and reduce risks of related complications as well as medical burdens. Umbilical cord derived mesenchymal stem cells exosomes (UCMSC-Exo), as the key effector of the stem cells with multipotential, can widely act on the functional cell units of bone marrow microenvironment and promote the repairment and regeneration of key cells such as hematopoietic stem cells, mesenchymal stem cells and endothelial cells, thus making it an ideal means for effectively promoting recovery of myelosuppression. Patients with acute myeloid leukemia who have achieved complete remission (CR) and are going to receive consolidation chemotherapy will be invited to participate in the study, to receive UCMSC-Exo intravenous infusion and follow-up visits of up to 1 years after enrollment.
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
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 and 60 years old;
- •Acute myeloid leukemia (AML, AML subtype M3 excluded) diagnosed according to the 2022 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia, who have achieved complete remission (CR1) and are going to receive consolidation therapy (cytarabine or cytarabine-based combined regimen, the cycle of consolidation therapy is not limited);
- •The participant or his/her legal guardian is adequately informed of the nature and risks of the study, voluntarily participates in the study with signed informed consent;
- •Male or female;
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 (by the day chemotherapy is initiated)
- •Estimated survival of at least 3 months;
- •Adequate major organ function:
- •Respiratory function: indoor oxygen saturation of at least 95%;
- •Cardiac function: ejection fraction of left ventricular of at least 45%;
- •Hepatic function: alanine aminotransferase/aspartate aminotransferase of at most 2.5 times/upper limit of normal value and serum total bilirubin of at most 1.5 times/upper limit of normal value;
- •Renal function: Serum creatinine of at most 1.5 times/upper limit of normal value;
- •Participants who do not receive any type of anti-cancer therapy within 2 weeks before enrollment (radiation therapy, chemotherapy and/or immune therapy, et al.), and treatment-associated toxicities induced by previous therapy has recovered to Grade 1 or below (except for low grade toxicities such as alopecia).
- •For female participants, they should be surgical sterilized or post-menopausal, or agree to utilize a medically recognised method of contraception (such as intrauterine device, condom) during treatment period of the study and within 6 months after the end of treatment period of the study; For male participants, they should be surgical sterilized or agree to utilize a medically recognised method of contraception (such as intrauterine device, condom) during treatment period of the study and within 6 months after the end of treatment period of the study;
排除标准
- •Central nervous system manifestations of acute myeloid leukemia at diagnosis;
- •Secondary acute myeloid leukemia;
- •Myelosuppression induced by conditions other than anti-cancer therapy;
- •Previous radiation therapy performed on sternum or pelvis;
- •Specifically diagnosed and uncontrolled infection at enrollment (Uncontrolled is defined as exhibiting ongoing signs and symptoms of infection without improvement despite anti-infective agents) ;
- •Uncontrolled active bleeding at enrollment;
- •Severe underlying comorbidities affecting survival, including cachexia, severe malnutrition, etc;
- •Estimated survival of at most 48 hours;
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
- •History of or current human immunodeficiency virus (HIV) infection;
- •Syphilis infection;
- •Continuous usage of immunosuppressants or received organ transplantation in the last 6 months;
- •Participation in clinical trials of other drugs within 6 weeks before enrollment;
- •Previous participation in clinical stem cell or exosome research;
- •Receive any agent concurrently with UCMSC-Exo infusion which inhibits cell division (hydroxyurea, low-dose cytarabine or methotrexate, etc) ;
- •Severe allergic constitution, or known or suspected allergy to the study drug and its components;
- •Known contraindication to receiving hematopoietic growth factors, transfusion of blood components, anti-infective agents;
- •Female participants who are pregnant or breast feeding;
- •Participants suffering from mental illness;
- •Presence of drug abuse/addiction;
- •History of other malignancies other than hematological malignancies within 3 years;
- •Participants without signed informed consent;
- •Participants with poor compliance and are unable to complete the whole course of the study;
- •Participants with circumstances that, in the opinion of the investigator, may increase the risk of the participants or interfere with conduct of the clinical trial and the judgment of results (excessive tension, sensitivity or cognitive impairment, etc) ;
- •Participants with other circumstances that are ineligible for enrollment in this study, in the opinion of the investigator.
研究组 & 干预措施
UCMSC-Exo intervention
UCMSC-Exo will be preset with 3 escalation dose levels in single time infusion.
干预措施: umbilical cord derived mesenchymal stem cells exosomes (UCMSC-Exo) (Biological)
结局指标
主要结局
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the day that UCMSC-Exo is infused to up to 28 days (short-term safety follow-up) and 1 year (long-term safety follow-up)
To investigate the safety characteristics, percentages will be calculated and grade will be evaluated.
Dose-limiting toxicities（DLT)
时间窗: From the day that UCMSC-Exo is infused to up to 14 days
During the DLT observation period, the subject has an adverse event that is reasonably related to UCMSC-Exo infusion (possibly, likely or definitely related).
Maximum tolerated dose (MTD)
时间窗: From the day that UCMSC-Exo is infused to up to 14 days
During the dose-escalation, the highest dose of dose-limiting toxicity for subjects no more than 1/6 in the dose group of at least 6 evaluable subjects of the study drug.
次要结局
- Incidence of febrile neutropenia(From the start of chemotherapy to up to 42 days)
- Duration of infection(From the start of chemotherapy to up to 42 days)
- Incidence of infection(From the start of chemotherapy to up to 42 days)
- Incidence of bleeding(From the start of chemotherapy to up to 42 days)
- Application rate of blood transfusion(From the start of chemotherapy to up to 42 days)
- Time to severe thrombocytopenia recovery(From the start of chemotherapy to up to 42 days)
- Time to absolute neutrophil count recovery(From the start of chemotherapy to up to 42 days)
- Duration of febrile neutropenia(From the start of chemotherapy to up to 42 days)
- Incidence of severe thrombocytopenia(From the start of chemotherapy to up to 42 days)
- Incidence of severe anemia(From the start of chemotherapy to up to 42 days)
- Time to severe anemia recovery(From the start of chemotherapy to up to 42 days)
- Application rate of anti-infective agents(From the start of chemotherapy to up to 42 days)
- Duration of bleeding(From the start of chemotherapy to up to 42 days)
研究者
Qiubai Li
M.D. & Ph.D., Professor
Wuhan Union Hospital, China