Effect of Stem Cell Infusion Time on aGVHD in Patients With Hematological Malignancies

A Multicenter Randomized Controlled Study of the Effect of Stem Cell Infusion Time on the Development of aGVHD in Patients With Hematological Malignancies After Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation

To observe the effect of stem cell infusion on the development of acute graft-versus-host disease (aGVHD) in patients with malignant hematologic diseases after allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT)

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Graft-versus-host Disease
• Intervention / Treatment: Procedure: Time of stem cell infusion

Detailed Description

Acute graft-versus-host disease (aGVHD) is a major complication and non-recurrent cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The human biological clock uses recurring environmental cues such as light and food intake to establish 24-hour rhythmic changes in sleep, hormone secretion, metabolism, body temperature, and immune function. Current clinical aGVHD prevention strategies focus on suppression of donor lymphocyte function by drugs or immunomodulatory cells, ignoring the impact of the recipient's own functional changes on the graft. The applicant's previous retrospective cohort study found that the time of stem cell infusion severely affected the incidence of aGVHD and its severity after allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT). Due to the lack of prospective clinical trial results on the effect of stem cell infusion time on the occurrence of aGVHD after allo-HSCT in the international arena, as well as the possible influence of multiple confounding factors in the aforementioned single-center retrospective study, the present study intends to randomize patients according to the time of stem cell infusion, and to observe its effect on the incidence of aGVHD, other transplant-related complications, and long-term survival after allo-PBSCT of patients with hematological malignancies.

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoyu Zhu, ph.D; Phone Number: 15255456091; Email: xiaoyuz@ustc.edu.cn
• Study Contact Backup: Name: Yue Wu, M.D; Phone Number: 13805601119; Email: wuyue20160701@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230036
      • The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Definite diagnosis of malignant hematologic disease before transplantation, age 12-60 years old, gender is not limited, race is not limited;
• Patients who are proposed to receive allo-PBSCT for the first time;
• Eastern Cooperative Oncology Group (ECOG) score 0-2;
• No serious organ failure and active infection;
• Voluntary open randomized controlled study to observe whether the time of stem cell infusion affects the occurrence of aGVHD after transplantation;
• Each subject must sign an informed consent form (ICF) indicating that he/she understands the purpose and procedures of the study and is willing to participate in the study; in view of the patient's condition, if the patient's own signature is not conducive to the treatment of his/her condition, the ICF will be signed by the legal representative.

Exclusion Criteria:

• Those with severe organ dysfunction or disease, such as severe disease and dysfunction of the heart, liver, kidneys and pancreas;
• Pregnant patients;
• Patients and/or authorized family members who refuse to undergo an open randomized controlled study to observe whether the time of stem cell infusion affects the occurrence of aGVHD after transplantation;
• Any life-threatening disease, physical condition, or organ system dysfunction that, in the opinion of the investigator, may compromise patient safety and put the results of the study at unnecessary risk; drug-dependent individuals; patients with uncontrolled psychiatric disorders; and individuals with cognitive dysfunction;
• Participants in other clinical studies that may affect aGVHD within 3 months;
• Those whom the investigator considers unsuitable for enrollment (e.g., those who anticipate that patients will not be able to adhere to the examination and treatment due to financial and other issues).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: the early infused group; infused stem cell within 11:30 am and 12:30 am	Procedure: Time of stem cell infusion; Randomization of patients according to the time of stem cell infusion
Sham Comparator: the late infused group; infused stem cell within 5:30 pm and 6:30 pm	Procedure: Time of stem cell infusion; Randomization of patients according to the time of stem cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of grade III to IV aGVHD	The primary endpoint of the study will be the development of aGVHD in the first 100 days post-transplant. Acute GVHD was graded according to the Mount Sinai Acute GVHD International Consortium criteria.	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The cumulative incidence of neutrophil engraftment at 28 days after transplantation	neutrophil engraftment time was defined as the first of three consecutive days during which the neutrophil count was at least 0.5×10^9/L.	28 days
The cumulative incidence of platelet recovery at 100 days after transplantation	Platelet recovery is defined as independence from platelet transfusion for at least 7 days with a platelet count of more than ≥ 100 × 10^9/L.	100 days
The cumulative incidence of chronic GVHD at 360 days after transplantation	The severity of chronic GVHD was graded according to the 2014 NIH criteria.	360 days
The probability of GVHD-free, relapse-free survival(GRFS)	The composite endpoint of GRFS was defined as the first events occurring after transplantation among Grade III to IV aGVHD, moderate to severe cGVHD, relapse, or death for any reason.	360 days
The probability of disease-free survival(DFS)	The DFS was defined as the interval between transplantation and disease recurrence, death or the last follow-up date, whichever occurred first.	360 days
The probability of overall survival(OS)	The OS was determined to be the time from the first day of transplantation until death from any cause or the last follow-up date.	360 days
The incidence of grade II to IV aGVHD	The cumulative incidence of grade II to IV aGVHD in the first 100 days post-transplant. aGVHD was graded according to the Mount Sinai Acute GVHD International Consortium criteria.	100 days
The cumulative incidence of transplant-related mortality at 180 days after transplantation	The cumulative incidence of transplant-related mortality at 180 days after transplantation	180 days
The cumulative incidence of transplant-related mortality at 360 days after transplantation	The cumulative incidence of transplant-related mortality at 360 days after transplantation	360 days

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Xiaoyu Zhu, ph.D, The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Time of stem cell infusion
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease
• Other Study ID Numbers: infusion time & aGVHD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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