Clinical trial NCT05672420: Umbilical Cord Derived Mesenchymal Stem Cells for Treatment-induced Myelosuppression in Hematologic Malignancies
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hematologic Neoplasms
Neutropenia
Anemia
Thrombocytopenia
Infections
Bleeding
Keywords: umbilical cord derived mesenchymal stem cells
treatment-induced myelosuppression
neutropenia
anemia
thrombocytopenia
infections
bleeding
hematologic malignancies
leukemia
lymphoma
multiple myeloma
chemotherapy
targeted therapy
hematopoietic stem cell transplantation
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Wuhan TongJi Hospital
name: Wuhan Central Hospital
First posted: 2023-01-05
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Aged between 18 and 75 years old;
2. Either type of primary hematologic malignancies listed below:

   1. 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;
   2. AML or ALL participants who achieved remission and are going to receive consolidation therapy;
   3. Relapsed/refractory AML or ALL participants who are going to receive first re-induction therapy;
   4. 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;
3. 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;
4. Male or female;
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 (by the day anti-cancer therapy is initiated)
6. Estimated survival of at least 3 months;
7. Adequate major organ function:

   1. Respiratory function: indoor oxygen saturation of at least 95%;
   2. Cardiac function: ejection fraction of left ventricular of at least 45%;
   3. 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;
   4. Renal function: Serum creatinine of at most 1.5 times/upper limit of normal value;
8. 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 toxities such as alopecia).

Exclusion Criteria:

1. Overt central nervous system manifestations of hematologic malignancies at diagnosis;
2. Secondary hematological maligancies;
3. Body mass index (BMI) of more than 30 kg/m\^2;
4. Myelosuppression induced by conditions other than anti-cancer therapy;
5. Previous radiation therapy performed on sternum or pelvis;
6. Specifically diagnosed and uncontrolled infection at enrollment (Uncontrolled is defined as exhibiting ongoing signs and symptoms of infection without improvement despite anti-infective agents) ;
7. Uncontrolled active bleeding at enrollment;
8. Severe underlying comorbidities affecting survival, including cachexia, severe malnutrition, etc;
9. Estimated survival of at most 48 hours;
10. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
11. History of or current human immunodeficiency virus (HIV) infection;
12. Continuous usage of immunosuppressants or received organ transplantation in the last 6 months;
13. Participation in clinical trials of other drugs within 6 weeks before enrollment;
14. Previous participation in clinical stem cell research;
15. Receiving any agent concurrently with UC-MSCs infusion which inhibits cell division (hydroxyurea, low-dose cytarabine or methotrexate, etc) ;
16. Severe allergic constitution, or known or suspected allergy to the study drug and its components;
17. Known contraindication to receiving hematopoietic growth factors, transfusion of blood components, anti-infective agents;
18. Female participants who are pregnant or breast feeding;
19. Participants with fertility plan;

    Note: 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;
20. Participants suffering from mental illness;
21. Presence of drug abuse/addiction;
22. History of other malignancies other than hematological malignancies within 3 years;
23. Participants without signed informed consent;
24. Participants with poor compliance and are unable to complete the whole course of the study;
25. 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) ;
26. Participants with other circumstances that are ineligible for enrollment in this study, in the opinion of the investigator.

Primary outcomes:
measure: Dose-limiting toxicities（DLT)
timeFrame: 4 days after the last UC-MSCs dose, up to 12 days
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the day that the last UC-MSCs dose is used to up to 21 days
measure: Maximum tolerated dose (MTD)
timeFrame: From the day that the last UC-MSCs dose is used to up to 4 days
Secondary outcomes:
measure: Time to absolute neutrophil count recovery
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Incidence of febrile neutropenia
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Duration of febrile neutropenia
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Incidence of severe thrombocytopenia
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Time to severe thrombocytopenia recovery
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Incidence of severe anemia
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Time to severe anemia recovery
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Incidence of infetion
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Duration of infetion
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Incidence of bleeding
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Duration of bleeding
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Application rate of blood transfusion
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Application rate of anti-infective agents
timeFrame: From the start of anti-cancer therapy or completion of hematopoietic stem cell transplantation to up to 42 days
measure: Time to achievement of complete remission
timeFrame: From enrollment to up to 28 days
measure: Duration of complete remission
timeFrame: From enrollment to maximun up to 2 years
measure: Event free survival
timeFrame: From enrollment to maximun up to 2 years
measure: Overall survival
timeFrame: From enrollment to maximun up to 2 years
measure: Incidence of infusion reactions in 2 years
timeFrame: 2 years since the last UC-MSCs infusion
measure: Incidence of secondary tumor in 2 years
timeFrame: 2 years since the last UC-MSCs infusion
measure: Cumulative incidence of relapse of primary disease in 2 years
timeFrame: 2 years since the last UC-MSCs infusion
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Central Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Tongji Hospital
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Qiubai Li, Professor
role: STUDY_DIRECTOR
References: