Amimestrocel Injection for Preventing Severe Oral Mucositis in HSCT Patients

A Single-Arm, Single-Center Exploratory Study of Amimestrocel Injection for the Prevention of Gastrointestinal Mucositis Induced by Conditioning Regimens Containing TBI and/or Melphalan

This study aims to see if a single intravenous infusion of a cell therapy called Amimestrocel injection can help prevent severe mouth sores (oral mucositis) in patients receiving a stem cell transplant.

Patients getting a stem cell transplant often receive strong chemotherapy (with radiation and/or a drug called melphalan) that can cause painful mouth and gut sores, making eating difficult and increasing infection risk. Amimestrocel injection is made from human umbilical cord cells that may help reduce inflammation and promote healing.

About 22 adult patients scheduled for this type of transplant at one hospital in China will receive the infusion 1-2 days before their stem cell transplant. Researchers will closely check for mouth sores, pain, and side effects for the first 28 days, and continue safety monitoring for 100 days.

The main goal is to see if the treatment lowers the rate of severe (Grade 3-4) mouth sores. The study will also track pain levels, need for pain medication, diarrhea, time for blood counts to recover, and overall safety.

Background and Rationale:

Myeloablative conditioning regimens containing total body irradiation (TBI) and/or high-dose melphalan are standard prior to allogeneic hematopoietic stem cell transplantation (HSCT) but frequently cause severe gastrointestinal mucositis. This condition leads to significant morbidity, including pain, dysphagia, diarrhea, nutritional impairment, infection risk, prolonged hospitalization, and increased costs. Effective preventive strategies are limited. Mesenchymal stem cells (MSCs) have demonstrated immunomodulatory and tissue-repair properties via paracrine secretion of anti-inflammatory and growth factors, showing potential in mitigating mucosal injury in preclinical and early clinical contexts.

Study Design:

This is a single-arm, single-center, open-label, exploratory interventional study. It will enroll approximately 22 subjects to preliminarily evaluate the efficacy and safety of prophylactic Amimestrocel infusion.

Intervention:

Eligible patients will receive a single, fixed-dose intravenous infusion of Amimestrocel injection (6.0×10⁷ cells in 150 mL) within 24 to 48 hours after the last dose of cyclophosphamide (part of the standard conditioning regimen) and before the infusion of hematopoietic stem cells (Day 0).

Study Population:

Adults aged 18-65 years planned for myeloablative allogeneic HSCT with a TBI and/or melphalan-containing conditioning regimen, with adequate organ function and ECOG status 0-1. Key exclusions include active uncontrolled infection, allergy to MSCs, prior cell therapy, and pregnancy.

Endpoints and Assessments:

Primary Endpoint: Incidence of Grade 3-4 oral mucositis (assessed daily by WHO/NCI-CTCAE criteria) within 28 days post-transplant (Day 0 to +28).

Secondary Endpoints: Duration/severity of oral and gastrointestinal mucositis; oral pain (Numerical Rating Scale); opioid use; time to neutrophil engraftment (ANC ≥0.5×10⁹/L); incidence of adverse events and serious adverse events (monitored until Day +100).

Sample Size Justification:

The sample size of 22 is derived from an assumption of reducing the historical incidence of severe oral mucositis (71% based on literature) to 41% (30% absolute reduction), with 80% power and a two-sided alpha of 0.05, accounting for a 10% dropout rate.

Study Procedures Overview:

The process includes a screening period (Day -14 to -7), the investigational product infusion, an intensive observation phase (Day 0 to +28) with daily mucositis and pain assessments, and a safety follow-up phase until Day +100 for AE/SAE monitoring, GVHD, and survival status.

Inclusion Criteria:

1. Aged 18 to 65 years.
2. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplantation.
3. The conditioning regimen must contain total body irradiation (TBI) and/or melphalan.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Adequate organ function defined as:Left ventricular ejection fraction (LVEF) ≥ 50%.Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN).Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min.
6. Voluntarily signs the informed consent form.

Exclusion Criteria:

1. History of allergy to mesenchymal stem cells or any component of the Amimestrocel injection preparation.
2. Presence of active, uncontrolled bacterial, fungal, or viral infection.
3. History of other malignancies within the past 5 years, except for cured carcinoma in situ or basal cell skin cancer.
4. Pregnant or lactating women, or those planning pregnancy during the study period.
5. Previous receipt of any cell therapy product.
6. Severe psychiatric disorder or cognitive impairment that would limit the ability to provide informed consent or comply with study procedures.
7. Any condition that, in the investigator's judgment, makes the subject unsuitable for study participation.