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

NCT06171906 | Not Yet Recruiting Phase 4

• 1 other identifier: MSC4PGF
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

MSC

Keywords

allo-HSCT; PGF

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Infection rate

  20~40 days after transplantation

• graft-versus-host disease

  within the initial 30 to 60 days or further

• survival rate

  1 year after transplantation

Study Arms (1)

MSCs treatment group

EXPERIMENTAL

Biological: mesenchymal stromal cells

Interventions

mesenchymal stromal cells BIOLOGICAL

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

MSCs treatment group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Screening patients for allogeneic hematopoietic stem cell transplantation;
• No gender limit, age ≥18 years old and ≤60 years old;
• KPS score \>60 points, expected survival period \>3 months;
• Those without serious functional damage to important organs throughout the body;
• The patient has no other contraindications to hematopoietic stem cell transplantation
• Voluntary test and informed consent.

You may not qualify if:

• Have severe heart, kidney or liver dysfunction;
• Those combined with other malignant tumors need treatment;
• There are clinical symptoms of brain dysfunction or severe mental illness and the inability to understand or follow the research protocol;
• Patients who cannot be guaranteed to complete the necessary treatment plan and follow-up observation;
• Patients with severe acute allergic reactions;
• Clinically uncontrolled active infection;
• Patients who are participating in other clinical trials;
• Researchers believe that the subject is not suitable for clinical trials for other reasons.

Sponsors & Collaborators

• ShiCang Yu: lead
• Xinqiao Hospital of Chongqing: collaborator

Study Sites (2)

Xinqiao Hospital

Chongqing, Shapingba District, 410000, China

Location

Second Affiliated Hospital, Army Medical University, PLA

Chongqing, China

Location

Related 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.

  PMID: 29392716 BACKGROUND

• 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.

  PMID: 29050516 BACKGROUND

Study Officials

• Lei Gao

  Xinqiao Hospital

  STUDY CHAIR

Central Study Contacts

Lei Gao, M.D., Ph.D.

CONTACT

023-68774330; gaolei7765@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: director of Stem cell and regenerative medicine

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: December 15, 2023
• Study Start: January 1, 2024
• Primary Completion: October 1, 2025
• Study Completion (Estimated): November 1, 2028
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)