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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06245746
• Other study ID #: UHCT231013
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: March 2024
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: Wuhan Union Hospital, China
• Contact: Qiubai Li, Professor
• Phone: 85726808
• Email: qiubaili[@]hust.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Anemia
• Bleeding
• Infections
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neutropenia
• Thrombocytopenia

Intervention

Biological:
• umbilical cord derived mesenchymal stem cells exosomes (UCMSC-Exo)
UCMSC-Exo will be infused intravenously.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	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
Secondary	Incidence of febrile neutropenia	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Secondary	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
Secondary	Incidence of severe thrombocytopenia	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Secondary	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
Secondary	Incidence of severe anemia	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Secondary	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
Secondary	Incidence of infection	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Secondary	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
Secondary	Incidence of bleeding	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Secondary	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
Secondary	Application rate of blood transfusion	To investigate the efficacy characteristics, percentages will be calculated.	From the start of chemotherapy to up to 42 days
Secondary	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