UCMSC-Exo for Chemotherapy-induced Myelosuppression in Acute Myeloid Leukemia

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Infections; Acute Myeloid Leukemia; Anemia; Bleeding; Thrombocytopenia; Neutropenia
• Intervention / Treatment: Biological: umbilical cord derived mesenchymal stem cells exosomes (UCMSC-Exo)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li, Professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn
• Study Contact Backup: Name: Di Wu; Phone Number: 86 18790696175; Email: 373181302@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged between 18 and 60 years old;
2. Acute myeloid leukemia (AML, AML subtype M3 excluded) diagnosed according to the 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia, who have achieved complete remission (CR) by cytarabine and daunorubicin/cytarabine and idarubicin induction chemotherapy and are going to receive consolidation chemotherapy by cytarabine;
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. Weight between 55 and 75kg;
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 (by the day chemotherapy is initiated)
7. Estimated survival of at least 3 months;

8. 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;
9. 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).
10. 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;

Exclusion Criteria:

1. Central nervous system manifestations of acute myeloid leukemia at diagnosis;
2. Secondary acute myeloid leukemia;
3. Myelosuppression induced by conditions other than anti-cancer therapy;
4. Previous radiation therapy performed on sternum or pelvis;
5. Specifically diagnosed and uncontrolled infection at enrollment (Uncontrolled is defined as exhibiting ongoing signs and symptoms of infection without improvement despite anti-infective agents) ;
6. Uncontrolled active bleeding at enrollment;
7. Severe underlying comorbidities affecting survival, including cachexia, severe malnutrition, etc;
8. Estimated survival of at most 48 hours;
9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
10. History of or current human immunodeficiency virus (HIV) infection;
11. Syphilis 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 or exosome research;
15. Receive any agent concurrently with UCMSC-Exo 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 suffering from mental illness;
20. Presence of drug abuse/addiction;
21. History of other malignancies other than hematological malignancies within 3 years;
22. Participants without signed informed consent;
23. Participants with poor compliance and are unable to complete the whole course of the study;
24. 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) ;
25. Participants with other circumstances that are ineligible for enrollment in this study, in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UCMSC-Exo intervention; UCMSC-Exo will be preset with 3 escalation dose levels in single time infusion.	Biological: umbilical cord derived mesenchymal stem cells exosomes (UCMSC-Exo); UCMSC-Exo will be infused intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	To investigate the safety characteristics, percentages will be calculated and grade will be evaluated.	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)
Dose-limiting toxicities（DLT)	During the DLT observation period, the subject has an adverse event that is reasonably related to UCMSC-Exo infusion (possibly, likely or definitely related).	From the day that UCMSC-Exo is infused to up to 14 days
Maximum tolerated dose (MTD)	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.	From the day that UCMSC-Exo is infused to up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to absolute neutrophil count recovery	To investigate the efficacy characteristics, time will be measured in days.	From the start of chemotherapy to up to 42 days
Incidence of febrile neutropenia	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Duration of febrile neutropenia	To investigate the efficacy characteristics, the duration will be measured in days.	From the start of chemotherapy to up to 42 days
Incidence of severe thrombocytopenia	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Time to severe thrombocytopenia recovery	To investigate the efficacy characteristics, time will be measured in days.	From the start of chemotherapy to up to 42 days
Incidence of severe anemia	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Time to severe anemia recovery	To investigate the efficacy characteristics, time will be measured in days.	From the start of chemotherapy to up to 42 days
Incidence of bleeding	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Duration of bleeding	To investigate the efficacy characteristics, the duration will be measured in days.	From the start of chemotherapy to up to 42 days
Application rate of blood transfusion	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Application rate of anti-infective agents	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Incidence of infection	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Duration of infection	To investigate the efficacy characteristics, the duration will be measured in days.	From the start of chemotherapy to up to 42 days

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Principal Investigator: Qiubai Li, Professor, Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: chemotherapy; bleeding; anemia; infections; neutropenia; acute myeloid leukemia; thrombocytopenia; chemotherapy-induced myelosuppression; umbilical cord derived mesenchymal stem cells exosomes
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Blood Platelet Disorders; Agranulocytosis; Leukopenia; Leukocyte Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neutropenia; Thrombocytopenia
• Other Study ID Numbers: UHCT231013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No