Graft-versus-host Disease, Hematological Malignancies
Conditions
Brief summary
The aim of this study is to evaluate the efficacy and safety of anti-thymocyte globulin combined with PTCy (post-HSCT cyclophosphamide, PTCy) in preventing graft-versus-host disease (GVHD) in allo-HSCT patients after anti-PD-1(anti-programmed cell death protein 1) antibody treatment. In this study, patients with hematological malignancies who needed to receive allo-HSCT after PD-1 antibody treatment were selected as the research subjects. Fludarabine and Busulfan was used as the conditioning regimen, and the dose of ATG (anti-thymocyte globulin, ATG) combined with PTCy was used as the GVHD prevention regimen. The aim of this study is to reduce the incidence of Regimen-Related Toxicity and GVHD without affecting engraftment and relapse, thereby reducing non-relapse mortality and further improving the survival of patients.
Detailed description
ATG (anti-thymocyte globulin, rabbit; 5 mg/kg, day -5 to -2) was used in matched sibling donor-HSCT. ATG (1.5 mg/kg, day -5; 2.5 mg/kg, day -4; mathematical function was then exploited to determine the total targeted ATG dose on day -3 to -2 based on concentrations of active ATG on day -5 to -4) was used in both haploidentical donor-HSCT and unrelated donor-HSCT. Reduced-dose PTCy regimen: two doses of 14.5 mg/kg Cy were given on days +3 and +4 post-HSCT.
Interventions
DRUGCyclophosphamid
ATG (anti-thymocyte globulin, rabbit; 5 mg/kg, day -5 to -2) was used in matched sibling donor-HSCT. ATG (1.5 mg/kg, day -5; 2.5 mg/kg, day -4; mathematical function was then exploited to determine the total targeted ATG dose on day -3 to -2 based on concentrations of active ATG on day -5 to -4) was used in both haploidentical donor-HSCT and mismatched unrelated donor-HSCT. Reduced-dose PTCy (two doses of 14.5 mg/kg Cy was given on days +3 and +4 post-HSCT) was used of GVHD prophylaxis.
Sponsors
Beijing 302 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* (1) age ≥ 18 years old, regardless of gender; * (2) patients with hematological malignancies (including lymphoma, leukemia, myelodysplastic syndrome, etc.) who had received at least one course of PD-1 antibody treatment; * (3) patients with indications for allo-HSCT, available donors (including matched sibling donors, haploidentical donors and unrelated donors), and no contraindications for transplantation; * (4) patients suitable for conventional Bu/Flu conditioning regimen; * (5) no serious heart, liver, kidney, lung and other important organ diseases; * (6) Eastern Cooperative Oncology Group (ECOG) performance status score 0-2; * (7) Hematopoietic stem cell transplantation comorbidity index (HCT-CI) score was 0-3; * (8) expected survival time of at least 12 weeks; * (9) women who are not pregnant or breastfeeding; * (10) voluntary participation in clinical research; They or their legal guardians were fully aware of the study and signed informed consent. Willing to follow and complete all trial procedures;
Exclusion criteria
* (1) pregnant or lactating women; * (2) other serious conditions that may limit enrollment (e.g., advanced infection, etc.); * (3) unable to understand and follow the study protocol or sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| acute graft-versus-host disease | 100 days | Acute graft-versus-host disease severity is usually graded (grades 0-IV) by the pattern of organ involvement using the classic Glucksberg-Seattle criteria (GSC). Higher grades mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| recurrence free survival | 1-year | Recurrence Free Survival is defined as the time interval between the day of reference in the study (date of randomization, date of diagnosis, etc.) and the date of local relapse/recurrence or regional relapse/recurrence or death (all causes) whichever occurs first. |
| non-relapse mortality | 1-year | Non-relapse mortality was defined as death from any cause other than malignancy relapse. |
| cumulative incidence of relapse | 1-year | cumulative incidence of relapse was measured from the date of transplantation until the date of hematologic relapse. |
| chronic graft-versus-host disease | 1-year | The National Institutes of Health scoring system (National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report) was used to define chronic GVHD. The standardization provided by the National Institutes of Health (NIH) 2005 and 2014 consensus projects has helped improve diagnostic accuracy and severity scoring (including grades mild, moderate, and severe) for clinical trials. Higher scores mean a worse outcome. |
| GVHD-free/ relapse-free survival | 1-year | GVHD-free/ relapse-free survival events were defined as grade 3-4 aGVHD or cGVHD requiring systemic immunosuppressive treatment, disease relapse, or any-cause death during the first 12 months after allogeneic HCT. |
| PD-L1 expression in acute myeloid leukemia bone marrow cells | Up to 1 year post-treatment | The expression levels of PD-L1 in acute myeloid leukemia bone marrow cells will be assessed at the 28th day after each medication cycle. |
| overall survival | 1-year | The time from transplantation to any cause death or the last follow-up was defined as overall survival. |
Contacts
Primary ContactXiaoning Gao, Doctor
Backup ContactYuxin Wang, Doctor
Outcome results
None listed