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

Official title

Prospective Randomized Controlled Phase III Clinical Study on the Impact of Stem Cell Infusion Timing on the Incidence of Acute Graft-versus-host Disease in Patients With Hematologic Malignancies Following Single-unit Umbilical Cord Blood Transplantation

Overview

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 single-unit unrelated cord blood transplantation (sUCBT).

Detailed description

Acute graft-versus-host disease (aGVHD) is a major complication and cause of non-relapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The human circadian clock utilizes recurring environmental cues such as light exposure and food intake to establish 24-hour rhythmic variations in sleep, hormone secretion, metabolism, body temperature, and immune function. Current clinical strategies for aGVHD prevention primarily focus on pharmacological or immunomodulatory suppression of donor lymphocyte activity, often overlooking the impact of recipient physiological fluctuations on graft outcomes. Our preliminary studies revealed that the timing of stem cell infusion significantly influences the incidence and severity of aGVHD after sUCBT. Given the lack of prospective clinical trial data internationally regarding the effect of infusion timing on aGVHD development post-allo-HSCT, coupled with potential confounding factors in existing retrospective studies and pilot experiments, this study proposes to randomize patients based on umbilical cord blood infusion timing. The investigation will evaluate how infusion time affects aGVHD incidence, other transplantation-related complications, and long-term survival rates in hematologic malignancy patients undergoing sUCBT.

Interventions

• Procedure Time of umbilical cord blood infusion
  Randomization of patients according to the time of umbilical cord blood infusion

Primary outcome measures

• The incidence of grade III to IV aGVHD [Time frame: 100 days post transplantation]

Secondary outcome measures (9)

• The incidence of grade II to IV aGVHD [Time frame: 100 days post transplantation]
• The cumulative incidence of neutrophil engraftment at 42 days after transplantation [Time frame: 42 days post transplantation]
• The cumulative incidence of platelet engraftment at 60 days after transplantation [Time frame: 60 days post transplantation]
• The cumulative incidence of transplant-related mortality at 360 days after transplantation [Time frame: 360 days post transplantation]
• The cumulative incidence of relapse at 360 days after transplantation [Time frame: 360 days post transplantation]
• The cumulative incidence of overall chronic GVHD at 360 days after transplantation [Time frame: 360 days post transplantation]
• The probability of GVHD-free, relapse-free survival(GRFS) [Time frame: 360 days post transplantation]
• The probability of disease-free survival(DFS) [Time frame: 360 days post transplantation]
• The probability of overall survival(OS) [Time frame: 360 days post transplantation]

Eligibility criteria

Inclusion criteria

• Definite diagnosis of malignant hematologic disease before transplantation, age, gender and race are not limited;
• Participants were required to have achieved complete remission with negative minimal residual disease (MRD) prior to transplantation;
• Participants who are proposed to receive sUCBT 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 subject's condition, if the participant'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;
• Any life-threatening disease, physical condition, or organ system dysfunction that, in the opinion of the investigator, may compromise participant safety and put the results of the study at unnecessary risk; drug-dependent individuals; participants 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• The First Affiliated Hospital of University of Science and Technology of China (Anhui Prov — Hefei

Identifiers

NCT: NCT07047456 · infusion time & UCBT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗