A Multicenter, Phase Ib/II Trial of the Safety and Efficacy of Umbilical Cord Derived Mesenchymal Stem Cells in Treatment-induced Myelosuppression in Patients With Hematologic Malignancies (USMYE Trial)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Hematologic Neoplasms
- Sponsor
- Wuhan Union Hospital, China
- Enrollment
- 181
- Locations
- 3
- Primary Endpoint
- Dose-limiting toxicities（DLT)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of the study is to explore the safety and efficacy of umbilical cord derived mesenchymal stem cells in treatment-induced myelosuppression in patients with hematologic malignancies.
Detailed Description
Despite the improved prognosis of patients with hematologic malignancies, almost all patients will experience severe myelosuppression induced by anti-cancer treatment, 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 interrruptions of anti-cancer treatment, failure of hematopoietic stem cell transplantation, and also patients' 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 (UC-MSCs), as a kind of 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 hematologic malignancies and treatment-induced myelosuppression will be invited to participate in the Phase Ib/II study, to receive UC-MSCs intravenous infusion and follow-up visits of up to 2 years after enrollment.
Investigators
Qiubai Li
M.D. & Ph.D., Professor
Wuhan Union Hospital, China
Eligibility Criteria
Inclusion Criteria
- •Aged between 18 and 75 years old;
- •Either type of primary hematologic malignancies listed below:
- •Acute myeloid leukemia (AML, AML subtype M3 excluded) or acute lymphoblastic leukemia (ALL) diagosed according to the 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia, either treatment naive participants who are going to receive first induction therapy, or participants who failed first induction therapy and are going to receive re-inducton therapy;
- •AML or ALL participants who achieved remission and are going to receive consolidation therapy;
- •Relapsed/refractory AML or ALL participants who are going to receive first re-induction therapy;
- •Phase II trial will also include: participants with primary hematological maligancies who are going to receive autologous hematopoietic stem cell transplantation (allo-HSCT) whereas are poor mobilizers (CD34+cell count in peripheral blood was below 11-19/μL before collection, or the amount of CD34+ cells transfused was below 2×10\^6/kg in allo-HSCT), and the participants' peripheral superficial veins have smooth blood flow which can meet the demand for intravenous drip;
- •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 anti-cancer therapy is initiated)
- •Estimated survival of at least 3 months;
Exclusion Criteria
- •Overt central nervous system manifestations of hematologic malignancies at diagnosis;
- •Secondary hematological maligancies;
- •Body mass index (BMI) of more than 30 kg/m\^2;
- •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;
Outcomes
Primary Outcomes
Dose-limiting toxicities（DLT)
Time Frame: 4 days after the last UC-MSCs dose, up to 12 days
During the DLT observation period, the subject has an adverse event that is reasonably related to UC-MSCs infusion (possibly, likely or definitely related).
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From the day that the last UC-MSCs dose is used to up to 21 days
To investigate the safety characteristics, percentages will be calculated and grade will be evaluated.
Maximum tolerated dose (MTD)
Time Frame: From the day that the last UC-MSCs dose is used to up to 4 days
During the dose-escalation phase, the highest dose of dose-limiting toxicity for subjects less than or equal to 1/3 in the dose group of at least 6 evaluble subjects of the study drug after the last UC-MSCs dose.
Secondary Outcomes
- Incidence of febrile neutropenia(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Duration of febrile neutropenia(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Duration of infetion(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Duration of bleeding(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Time to absolute neutrophil count recovery(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Time to severe anemia recovery(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Incidence of bleeding(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Application rate of blood transfusion(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Time to achievement of complete remission(From enrollment to up to 28 days)
- Incidence of secondary tumor in 2 years(2 years since the last UC-MSCs infusion)
- Incidence of severe thrombocytopenia(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Time to severe thrombocytopenia recovery(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Incidence of severe anemia(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Overall survival(From enrollment to maximun up to 2 years)
- Incidence of infetion(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Incidence of infusion reactions in 2 years(2 years since the last UC-MSCs infusion)
- Cumulative incidence of relapse of primary disease in 2 years(2 years since the last UC-MSCs infusion)
- Event free survival(From enrollment to maximun up to 2 years)
- Application rate of anti-infective agents(From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days)
- Duration of complete remission(From enrollment to maximun up to 2 years)