AML, Elderly
Conditions
Keywords
Haplo-HSCT, elderly, AML, RIC
Brief summary
Elderly AML patients receiving conventional chemotherapy have poor prognosis. Allo-HSCT offers better long-term survival than chemotherapy, while high TRM limits its use. Current research focuses more on improving conditioning regimens to reduce TRM. Studies suggest Bu/Flu/Cy/ATG are safer and more effective for elderly AML haplo-HSCT, lowering TRM. However, prospective randomized trials are lacking. This study aims to compare Bu/Flu/Cy/ATG vs. Bu/Cy/ATG to determine if TRM can be reduced in elderly AML undergoing haplo-HSCT.
Detailed description
The prognosis of elderly patients with acute myeloid leukemia (AML) undergoing conventional chemotherapy is poor. Compared with chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve long-term survival in elderly patients. However, the high transplantion-related mortality (TRM) limited its application. Currently, the top priority in transplantation for elderly AML patients is to reduce TRM through methods such as optimizing conditioning regimens, reducing graft-versus-host disease (GVHD), and preventing infections. Present research primarily focuses on optimizing conditioning regimens. Both domestic and international studies, as well as our team's preliminary research, suggest that replacing cyclophosphamide (Cy) with fludarabine (Flu) can reduce toxicity. Earlier prospective single-arm clinical study in our team confirmed that the Bu/Flu/Cy/ATG regimen is a safe and effective conditioning protocol for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in elderly AML patients. This study aims to use a prospective randomized controlled trial to verify whether the Bu/Flu/Cy/ATG conditioning regimen can reduce TRM compared with the Bu/Cy/ATG regimen in elderly AML patients undergoing haplo-HSCT.
Interventions
PROCEDUREBu/Flu/Cy/ATG
The Bu/Flu/Cy/ATG conditioning regimen consists of the following components: Ara-C (2 g/m²/day, injected i.v.) on days-10 and-9; Bu (0.8 mg/kg, q6h, injected i.v.) on days -8 to -6; Flu (30 mg/m²/day, injected i.v.) from day-6 to day-2; Cy (1.0 g/m²/day, injected i.v.) on days-5 and-4; and ATG (2.5 mg/kg/day) on days-5 to -2.
PROCEDUREBu/Cy/ATG
The Bu/Cy/ATG conditioning regimen consists of the following components: Ara-C (4 g/m²/day, injected i.v.) on day-9; Bu (0.8 mg/kg, q6h, injected i.v.) on days -8 to -6; Cy (1.8 g/m²/day, injected i.v.) on days-5 and-4; and ATG (2.5 mg/kg/day) on days-5 to -2.
Sponsors
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- (a)Diagnosed with AML in first complete remission (CR1). (b)Age ≥55 years. (c)Availability of an haploidentical donor, first transplant, no matched sibling or unrelated donor. (d)Willingness to provide written informed consent.
Exclusion criteria
* (a) Uncontrolled active infection. (b) Secondary AML. (c)Refusal to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transplant-related mortality (TRM) | From HSCT to the follow-up assessment at 12 months post-treatment. | TRM is defined as death due to any transplantation-related cause other than disease relapse. Transplant-related mortality will be calculated using a competing risks model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of conditioning | From HSCT to the follow-up assessment at 28 days and 100 days post-treatment. | Toxicity of conditioning within 28 days of HSCT can be graded according to Common Terminology Criteria for Adverse Events (CTCAE): 1.Grade 1: Mild toxicity that does not require medical intervention. 2.Grade 2: Moderate toxicity that may require medical intervention. 3.Grade 3: Severe toxicity that requires significant medical intervention, hospitalization, or results in lasting effects. 4.Grade 4: Life-threatening toxicity, potentially requiring intensive care. 5.Grade 5: Death caused by the toxicity reaction. |
| Engraftment | Platelet engraftment was assessment at 28 days post-transplantation. | Platelet engraftment was defined as the first of seven consecutive days with a platelet count \>20 × 109/L without transfusion support. Neutrophil engraftment was defined as the first of three consecutive days with an ANC \> 0.5 × 109/L. |
| GVHD | From HSCT to the follow-up assessment at 12 months post-treatment. | Acute GVHD was classified as symptom presentation before 100 days after haplo-HSCT and chronic GVHD was classified as symptom presentation \>100 days after haplo-HSCT. Each organ (skin, liver, and gut) was staged 1 through 4 for Acute GVHD according to modified criteria based on the schema of the Mount Sinai Acute GVHD International Consortium (MAGIC), and patients were also assigned a grade of acute GVHD (I through IV) based on overall severity. Chronic GVHD was graded in accordance with the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease Consensus Criteria. |
| Overall Survival | From HSCT to the follow-up assessment at 12 months post-treatment. | The time from haplo-HSCT to death from any cause in patients with AML. Overall survival will be calculated using the Kaplan-Meier method. |
| Cumulative Incidence of Relapse | From HSCT to the follow-up assessment at 12 months post-treatment. | Relapse was defined as disease recurrence. |
| Leukemia-free survival | From HSCT to the follow-up assessment at 12 months post-treatment. | Leukemia-free survival (LFS) was defined as the time from transplantation to relapse, disease progression, or death, whichever occurred first. |
| Event-Free Survival | From HSCT to the follow-up assessment at 12 months post-treatment. | Event-Free Survival (EFS) was defined as the time from transplantation to relapse, graft failure, death from any cause, or requirement for additional anti-leukemic therapy. |
| Viral Infection | From HSCT to the follow-up assessment at 12 months post-treatment. | Detection of CMV-DNA and EBV-DNA in peripheral blood twice a week. |
Countries
China
Contacts
CONTACTYuqian Sun
Outcome results
None listed