Background and Significance:

Graft-versus-host Disease(GVHD) is still an important issue need to further discuss in patients undergo haploidentical hematopoietic stem cell transplantation(haplo-HSCT) for its high mortality and increased economic burden of patients. In recent years, numerous clinical trials try to improve the prophylaxis strategy to balance GVHD, engraftment, immune reconstitution, relapse and infection. Antithymocyte globulin(ATG)-based haplo-HSCT system is widely accept as an effective prophylaxis regimen but accompany with relatively high rate of GVHD and infection. Anti-CD25 monoclonal antibody has been proved effective for steroid-refractory acute GVHD(aGVHD), but its effectiveness in GVHD prophylaxis is still not clear.

Our previous research indicated that low-dose ATG (7.5mg/kg) in the conditioning regimen can further reduce EBV and CMV affection compared with 10mg/kg ATG, while didn't impaire the effect of GVHD prophylaxis. But the grade III to IV aGVHD and chronic GVHD(cGVHD) were still relatively high and with no significantly difference between 7.5mg/kg ATG group and 10mg/kg ATG group. Here, we designed this clinical trial to identify the effect of combined CD25 antibody and low-dose ATG for GVHD prophylaxis in haploid transplantation.

Study Design and Methods:

This is a multi-center, non-randomized phase 2 clinical trial in China from March 2024 to March 2026 to investigate whether the combination of low-dose ATG and CD25 monoclonal antibody will be more effective than low-dose ATG alone in GVHD prophylaxis. The trial was registered at www.clinicaltrials.gov as #NCT06334367. We plans to recruit 40 adult patients(18 to 60 years old) with malignant hematological disease and will undergo haplo-HSCT. And patients will be assigned in a 1:1 ration to accept low-dose ATG or low-dose ATG combined CD25 antibody for GVHD prophylaxis.

Patients in both groups received intravenously administered ATG at a dose of 2.5mg/kg daily from day -4 to day -2. In the CD25 group, patients will inject intravenously with human-anti-CD25 monoclonal antibody at a dose of 1mg/kg on day +4 and +7.

The inclusion Criterias are as follows:(1)patients diagnose of hematologic disease, weighing ≥30kg, aged 18-60, of any gender and race; (2)willing to undergo haploidentical HSCT; (3)voluntarily participate in this study. The exclusion Criteria are as follows:(1)those with severe organ dysfunction or diseases, such as heart, liver, kidney, and pancreatic diseases; or other conditions that the researcher believes not suitable to the study; drug dependence; uncontrolled mental illness; cognitive dysfunction; (2)Patients who cannot tolerate CD25 monoclonal antibody treatment; (3)subjects and/or authorized family members who refuse allo-HSCT treatment; (4)those who have participated in other similar clinical studies within the past 3 months; (5)those deemed unsuitable for inclusion by the researcher (such as patients expected to be unable to adhere to treatment due to financial issues, etc.).

Baseline characteristics will be summarized using descriptive statistics. The cumulative incidence rates and overall survival will be estimated using Cox regression model and Kaplan-Meier method respectively.

Statistical methods:

The primary endpoint is the occurrence of aGVHD and cGVHD at 100days and 1 year after HSCT, respectively. Other outcome measurement include the time of donor cell engraftment and immune reconstitution, infection, disease relapse or progression, and death from any cause.

Disclosures

No relevant conflicts of interest to declare.

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2024
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