Poor Graft Function
Conditions
Keywords
poor graft function, hematopoietic stem cell transplantation
Brief summary
This randomized trial aims at validating the efficacy and safety of low-dose decitabine for PGF post allo-HSCT.
Detailed description
Poor graft function (PGF), defined by the presence of multilineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (allo-HSCT). Emerging evidence demonstrates that the inadequate stem cells infusion, bone marrow microenvironment and immune dysregulation play a crucial role in maintaining and regulating hematopoiesis. Current therapies remain debatable, including selected CD34+ cells infusion, mesenchymal stromal cells infusion, prophylactic N-acetyl cysteine administration, etc. Thereafter, the investigators conduct a randomized trial aiming at validating the efficacy and safety of low-dose decitabine in PGF post allo-HSCT patients.
Interventions
DRUGDecitabine
Decitabine 6 mg/m2 daily subcutaneously for consecutive 3 days (day 1 to day 3)
DRUGGranulocyte Colony-Stimulating Factor
5ug/kg/d when absolute neutrophil count ≤ 1.5 × 109/L
Eltrombopag initial dose: 25 mg orally once a day, may increase to up to 75 mg/day, when platelet count ≤ 30 × 109/L; Avatrombopag initial dose: 20 mg orally once a day, may increase to up to 60 mg/day, when platelet count ≤ 30 × 109/L.
DRUGRecombinant human erythropoietin
10000 U/day when hemoglobin ≤ 85 g/L
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed as PGF at day 28 post-HSCT or later. PGF was defined as two or three cytopenias, absolute neutrophil count ≤ 1.5 × 109/L, platelet count ≤ 30 × 109/L, hemoglobin ≤ 85g/L, lasting for more than 2 consecutive weeks; 2. Full donor chimerism; 3. Primary disease in remission; 4. No severe GVHD and relapse; 5. ECOG: 0-2; 6. Expected survival longer than 1 month
Exclusion criteria
1. Allergic to decitabine; 2. Active infections; 3. Uncontrolled GVHD; 4. Severe organ dysfunction; 5. Relapse of underlying malignancies; 6. Graft failure; 7. Received decitabine or participated in other clinical trials within one month before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Treatment Response (Hematological Response + Hematological Improvement) | day +28 | Hematological response (HR) was defined as recovery in all cell lineages (neutrophils ≥ 1.5 x 109/L, platelets ≥ 30 x 109/L and hemoglobin ≥ 85 g/L) without the need for transfusion or growth factor support for consecutive 7 days. Hematological improvement (HI) was defined as recovery of at least 1 lineage. No response (NR) refers to those who failed to reach HR or HI. |
| Overall Survival Rate | 1 year | Overall survival was calculated from time of random assignment to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bone Marrow Recovery | day +28 | Bone marrow recovery was assessed using quantitative morphometric analysis to determine marrow cellularity, the myeloid-to-erythroid ratio, and megakaryocyte counts. |
| Number of Participants With Relapse | 3-month | Relapse was defined according to the European LeukemiaNet (ELN) guidelines |
| Event Free Survival Rate | 1 year | EFS referred to time from random assignment to disease progression /relapse, severe bleeding events, severe infections or death from any cause. |
| Number of Participants With GVHD | 3-month | Diagnosis and grading of GVHD was performed according to NCCN Clinical Practice Guidelines, 2020 |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYue Han, Professor
The First Affiliated Hospital of Soochow University
Participant flow
Recruitment details
Between July 01, 2023, and January 01, 2026, a total of 126 patients were screened, and 76 were enrolled in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants |
| Age, Continuous | 47 year |
| Number of participants with neutropenia, anemia and thrombocytopenia | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 51 | 9 / 25 |
| other Total, other adverse events | 28 / 51 | 16 / 25 |
| serious Total, serious adverse events | 0 / 51 | 1 / 25 |
Outcome results
None listed