Umbilical Cord Derived Mesenchymal Stem Cells for Treatment-induced Myelosuppression in Hematologic Malignancies

Huazhong University of Science and Technology

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Anemia; Hematologic Neoplasms; Thrombocytopenia; Neutropenia; Infections; Bleeding

Treatments: Biological: umbilical cord derived mesenchymal stem cells

Study type: Interventional

Funder types: Other

Identifiers

NCT05672420

UHCT22668

Details and patient eligibility

About

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.

Full 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.

Enrollment: 181 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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181 participants in 1 patient group

umbilical cord derived mesenchymal stem cells (UC-MSCs)

Experimental group

Description:

In the Phase Ib study, participants will be those with treatment-induced myelosuppression and acute myeloid leukemia/acute lymphoblastic leukemia, UC-MSCs will be preset with 5 escalation dose levels: dose A , dose B, dose C ,dose D and dose E, frequency of infusion will be preset with 3 escalation levels: frequency 1, frequency 2, frequency 3, total course of treatment: 2 weeks; In the Phase II study, participants will be those with treatment-induced myelosuppression and acute myeloid leukemia/acute lymphoblastic leukemia/primary hematological maligancies who are going to receive hematopoietic stem cell transplantation, UC-MSCs will be preset according to the recommended phase II dose (RP2D) from the Phase Ib study, total course of treatment: 2 weeks.

Treatment:

Biological: umbilical cord derived mesenchymal stem cells