Phase I Clinical Study of Haplo-HSCT Combined With Hypoxic 3D-Cultured Umbilical Cord MSC for the Treatment of SAA

Efficacy and Safety of Sequential Infusion of Hypoxic 3D-Cultured Umbilical Cord Mesenchymal Stem Cells in Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multicenter, Randomized, Phase 1 Trial

Efficacy and Safety of Sequential Infusion of Hypoxic 3D-Cultured Umbilical Cord Mesenchymal Stem Cells in Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multicenter, Randomized, Phase 1 Trial

Study Overview

• Status: Enrolling by invitation
• Conditions: Severe Aplastic Anemia; Severe Aplastic Anemia (SAA); Severe Aplastic Anemia, Refractory
• Intervention / Treatment: Drug: 3D hypoxia-preconditioned UC-MSC group; Drug: 2D UC-MSC group

Detailed Description

The enrolled patients with an HLA-haploidentical relative for HSCT received the fludarabine (Flu) + cyclophosphamide (Cy) + antithymocyte globulin (ATG) conditioning regimen. For the patients with acute SAA (SAA-I), intravenous administration of 30 mg/(m2 day) of Flu and 500-800 mg/(m2 day) of Cy was performed from days -5 to -2, and 5μg/(kg day) of ATG was administered from days -4 to -1. For the patients with chronic SAA (SAA-II), the same treatment of ATG and Cy was applied as above with the supplement of 0.6 mg/(kg 6 h) of busulfan (BU) from days -8 to -5 prior to transplantation. Donor selection and hematopoietic stem cell mobilization and collection were conducted based on the consensus of The Chinese Society of Hematology regarding indications, conditioning regimens, and donor selection for allogeneic hematopoietic stem cell transplantation. On day 0, HSCs were infused intravenously. Both groups received 5 × 10⁵/kg UC-MSCs at 4 h before HSC infusion. The control group was transfused with conventional 2D-cultured UC-MSCs, whereas the experimental group received 3D hypoxia-preconditioned UC-MSCs. Standard GVHD prophylaxis consisted of mycophenolate mofetil, cyclosporine A, and methotrexate (MTX).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100853
    • 28 Fuxing Road, Beijing, China.

Participation Criteria

Eligibility Criteria

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

Description

The inclusion criteria were (1) age 6 to 60 years; (2) diagnosis of SAA or very SAA according to the International Aplastic Anemia Study Group[21]; (3) without any severe pulmonary, cardiac, liver, or renal diseases or any active infection; and (4) adequate performance status (Eastern Cooperative Oncology Group score 0-2). Exclusion Criteria：(1)Age 6 years or > 60 years; (2)Failure to meet the IAASG-defined diagnosis of SAA/vSAA, or confirmed (3)Fanconi anemia, congenital aplastic anemia (e.g., dyskeratosis congenita, Diamond-Blackfan anemia); (4)Presence of severe pulmonary, cardiac, hepatic, or renal insufficiency; Uncontrolled active infection; (5)Eastern Cooperative Oncology Group (ECOG) performance status score ≥ 3.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3D hypoxia-preconditioned UC-MSC group	Drug: 3D hypoxia-preconditioned UC-MSC group; 5 × 10⁵/kg 3D hypoxia-preconditioned UC-MSCs at 4 h before HSC infusion
Active Comparator: 2D UC-MSC group	Drug: 2D UC-MSC group; 5 × 10⁵/kg 2D UC-MSCs at 4 h before HSC infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events	The incidence and severity of adverse events (AEs) within the first 150 days after haplo-HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of relapse		UP to 2 years after HSCT
The implantation	The implantation rate and implantation time.	Up to 4 weeks after HSCT
acute GVHD		100days after HSCT
chronic GVHD		1 years after HSCT
Surivial		1 year after HSCT

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: Beijing Friendship Hospital; Beijing 302 Hospital; The University of Hong Kong-Shenzhen Hospital; Shenzhen University General Hospital; Yan'an University Affiliated Hospital; The First Medical Center of Chinese PLA General Hospital; The Fourth Medical Center of Chinese PLA General Hospital; Pollon Life Co., Ltd.; Beijing GeniusCure Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: December 10, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; Hematopoietic Stem Cell Transplantation; Severe Aplastic Anemia
• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Hemic and Lymphatic Diseases; Anemia, Aplastic
• Other Study ID Numbers: S2021-384-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Treatment effect
• IPD Sharing Time Frame: 2025/10/1-2027/1/1
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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