Mesenchymal Stem Cells for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation

MSC Clinical Trial

Official title:

Clinical Study of MSCs for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06171906
• Other study ID #: MSC4PGF
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 1, 2024
• Est. completion date: November 1, 2028

Study information

• Verified date: December 2023
• Source: Southwest Hospital, China
• Contact: Lei Gao, M.D., Ph.D.
• Phone: 023-68774330
• Email: gaolei7765[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective approach for treating both benign and malignant blood disorders. It primarily involves high-dose chemotherapy to eliminate tumor cells within the patient's body, as well as to suppress the recipient's hematopoiesis and immune function. The transplantation replaces the recipient's original hematopoietic stem cells (HSCs) with donor-derived HSCs, thereby reconstructing the donor's hematopoietic and immune functions to achieve disease cure.

Poor graft function (PGF) following transplantation, which refers to inadequate engraftment of the transplanted hematopoietic stem cells, is one of the major factors limiting the effectiveness of allo-HSCT. Mesenchymal stromal cells (MSCs), identified within the bone marrow stroma, are a type of non-hematopoietic multipotent stem cells. Several studies, including previous research by our research team, suggest that MSCs can improve the bone marrow hematopoietic microenvironment by secreting various cytokines. This leads to the promotion of hematopoietic stem cell proliferation and differentiation, enhancement of hematopoietic function, and support for hematopoiesis as well as direct or indirect promotion of vascular regeneration in damaged tissues and organs.

Therefore, exploring the efficacy of umbilical cord-derived MSCs in treating poor graft function after allo-HSCT, observing the recovery of blood parameters in patients with poor engraftment, monitoring transplantation-related complications and immune reconstitution, and conducting preliminary investigations into the underlying mechanisms can contribute to the exploration of new clinical techniques for the treatment of PGF following allo-HSCT.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 68
• Est. completion date: November 1, 2028
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Screening patients for allogeneic hematopoietic stem cell transplantation;

2. No gender limit, age =18 years old and =60 years old;

3. KPS score >60 points, expected survival period >3 months;

4. Those without serious functional damage to important organs throughout the body;

5. The patient has no other contraindications to hematopoietic stem cell transplantation

6. Voluntary test and informed consent.

Exclusion Criteria:

1. Have severe heart, kidney or liver dysfunction;

2. Those combined with other malignant tumors need treatment;

3. There are clinical symptoms of brain dysfunction or severe mental illness and the inability to understand or follow the research protocol;

4. Patients who cannot be guaranteed to complete the necessary treatment plan and follow-up observation;

5. Patients with severe acute allergic reactions;

6. Clinically uncontrolled active infection;

7. Patients who are participating in other clinical trials;

8. Researchers believe that the subject is not suitable for clinical trials for other reasons.

Related Conditions & MeSH terms

• MSC

Intervention

Biological:
• mesenchymal stromal cells
On the basis of conventional PGF treatment for poor implantation, the enrolled patients were injected with 1×10^6/kg mesenchymal stem cells of cord blood weekly for 4 consecutive weeks

Locations

Country	Name	City	State
China	Second Affiliated Hospital, Army Medical University, PLA	Chongqing
China	Xinqiao Hospital	Chongqing	Shapingba District

Sponsors (2)

Lead Sponsor	Collaborator
ShiCang Yu	Xinqiao Hospital of Chongqing

Country where clinical trial is conducted

China, 

References & Publications (2)

Kong Y, Song Y, Tang FF, Zhao HY, Chen YH, Han W, Yan CH, Wang Y, Zhang XH, Xu LP, Huang XJ. N-acetyl-L-cysteine improves mesenchymal stem cell function in prolonged isolated thrombocytopenia post-allotransplant. Br J Haematol. 2018 Mar;180(6):863-878. doi: 10.1111/bjh.15119. Epub 2018 Feb 2. — View Citation

Michalicka M, Boisjoli G, Jahan S, Hovey O, Doxtator E, Abu-Khader A, Pasha R, Pineault N. Human Bone Marrow Mesenchymal Stromal Cell-Derived Osteoblasts Promote the Expansion of Hematopoietic Progenitors Through Beta-Catenin and Notch Signaling Pathways. Stem Cells Dev. 2017 Dec 15;26(24):1735-1748. doi: 10.1089/scd.2017.0133. Epub 2017 Nov 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Hemogram recovery of patients with poor graft function after treatment	White blood cells: neutrophil engraftment is defined as neutrophils exceeding 0.5×10^9/L for 3 consecutive days; red blood cells: hemoglobin is not less than 70g/L, and is free of blood transfusion; Platelets: Complete response is defined as platelet count =50×10^9/L, continuous for 7 days without platelet transfusion; Partial response (PR) is defined as platelet count (20~50)×10^9/L, continuous Weaning from platelet transfusion at 7 days; no response (NR) is defined as 8 weeks of use at the maximum tolerated dose, platelet count <20×10^9/L or not weaning from platelet transfusion	20~40 days after transplantation
Secondary	Infection rate	Unexpected problems that may occur to the patient or others	20~40 days after transplantation
Secondary	graft-versus-host disease	Graft-versus-host disease (GVHD) is a potentially serious complication of allogeneic stem cell transplantation and reduced-intensity allogeneic stem cell transplantation.	within the initial 30 to 60 days or further
Secondary	survival rate	1-year overall survival and disease-free survival	1 year after transplantation