Hematologic Disease
Conditions
Keywords
Hematopoietic cell transplantation, HLA mismatch, Hematologic diseases
Brief summary
This study is a single center, prospective, single arm exploratory clinical trial that includes patients with hematological malignancies who are indicated for allogeneic hematopoietic stem cell transplantation (allo HSCT) but lack suitable donors. This project plans to use highly mismatched unrelated HLA mismatched donors. Ultimately, an unrelated human leukocyte antigen (HLA) mismatched allo HSCT transplantation plan will be established to improve the disease prognosis of this group of patients and truly enter the era of everyone has a donor for allo HSCT.
Detailed description
This study is a single center, prospective, single arm exploratory clinical trial that includes patients with hematological malignancies who are indicated for allogeneic hematopoietic stem cell transplantation (allo HSCT) but lack suitable donors. This project plans to use highly mismatched unrelated HLA mismatched donors. Ultimately, an unrelated human leukocyte antigen (HLA) mismatched allo HSCT transplantation plan will be established to improve the disease prognosis of this group of patients and truly enter the era of everyone has a donor for allo HSCT.
Interventions
Myeloablative conditioning: Busulfan (Bu，3.2 mg/kg/d IV -8d \ -6d); Reduced intensity conditioning: Busulfan (Bu，3.2 mg/kg/d IV -7d\ -5d);
Myeloablative conditioning: Cyclophosphamide (Cy，1.8g/m2, -5d, -4d) Cyclophosphamide is not used for reduced intensity conditioning
Myeloablative conditioning: Fludarabine (Flu，30 mg/m2/d IV -6d \ -2d); Reduced intensity conditioning: Fludarabine (Flu，30mg/m2 /d IV -10d\ -5d);
For both myeloablative and reduced intensity conditioning: Semustine (MeCCNU: 250 mg/m2 orally-3d)
Sponsors
He Huang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients (18-60 years old) with hematological malignancies and indications for hematopoietic stem cell transplantation; * Non blood donors without human leukocyte antigen (HLA) high-resolution typing ≥ 9/10, or those who have difficulty finding non blood donors due to urgent medical conditions; * No suitable HLA matching haploidentical donor available; * There are suitable unrelated HLA mismatched (HLA high-resolution typing\<9/10) donors; * The subjects or their legal representatives shall sign an informed consent form before the start of the clinical study.
Exclusion criteria
* Patients with severe liver and kidney function (alanine aminotransferase\>2.5 times the upper limit of normal, blood creatinine\>1.5 times the upper limit of normal) and cardiopulmonary dysfunction (New York Heart Association (NYHA) III/IV heart function, ejection fraction\<50%, severe obstructive or restrictive ventilation dysfunction); * Merge active infections; * Eastern Cooperative Oncology Group Performance Status (ECOG) score ≥ 2 points; * Secondary tumors with merged activity; * Severe central nervous system or mental illness leading to the inability to autonomously choose to enter or exit clinical trials; * Combine other allo hematopoietic stem cell transplantation (HSCT) contraindications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 1-year | Overall survival (OS) after allogeneic hematopoietic cell transplantation is defined as the proportion of patients who are alive at a specified time point following the transplantation, regardless of disease status or cause of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet engraftment rate | 28-days | The 28-day platelet engraftment rate is assessed, with platelet engraftment defined as achievement of a platelet count of ≥ 20 × 10⁹/L without transfusion support for at least seven consecutive days. |
| GVHD | 180 days and 2 year | Cumulative incidence of aGvHD and cGvHD in different target organs and overall population. |
| Neutrophil engraftment rate | 28-days | The 28-day neutrophil engraftment rate is assessed, with neutrophil engraftment defined as achievement of an absolute neutrophil count (ANC) of ≥ 0.5 × 10⁹/L for three consecutive days. |
| Progression-free survival | 1-year | Progression-free survival (PFS) after allogeneic hematopoietic cell transplantation is defined as the length of time a patient survives without evidence of disease progression or relapse following the transplantation. |
| Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) | 1-year | Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation is defined as the time a patient survives without experiencing grade III-IV acute GVHD, severe chronic GVHD, relapse, or death. |
| Relapse | 1-year | Cumulative incidence of disease relapse after transplantation. |
Countries
China
Contacts
Primary ContactYishan Ye, MD., PhD
Outcome results
None listed