Acute Leukemia, Myelodysplastic Syndromes, Severe Aplastic Anemia (SAA)
Conditions
Keywords
Ruxolitinib, Sirolimus, Mycophenolate Mofetil, Graft-versus-host-disease, Haploidentical, Calcineurin Inhibitor
Brief summary
Graft-versus-host disease (GVHD) is an important complication after transplantation, with an incidence of 40-60%, which can increase non-relapse mortality if poorly controlled. At present, the standard prophylaxis for GVHD is cyclosporine combined with methotrexate. However, calcineurin inhibitors (CNI) can cause some vital side effects, which are not tolerated by some patients. Therefore, this study aims to explore the safety and efficacy of Sirolimus in combination with Ruxolitinib and Mycophenolate Mofetil for the prophylaxis of GVHD in patients with haplo-HSCT who are intolerant to calcineurin inhibitors.
Interventions
DRUGSirolimus
Sirolimus 2mg once daily, maintaining the concentration at 5-10 ng/ml. Gradually reduce the dosage after +100 days. If the patient has stable engraftment and no GVHD, discontinue on +180 days.
DRUGRuxolitinib
Ruxolitinib is administered at a dose of 5mg twice daily from the start of the study until +90 days. The dose is reduced to 5mg once daily on +90 days, and discontinued on +120 days.
DRUGMMF
MMF 0.5g, taken twice daily, is discontinued after 60 days. If it is resumed after 60 days, it should be taken for 2 weeks.
DRUGATG
2.5 mg/kg, from -5d to -2d
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary disease: hematological malignancies (including acute leukemia, myelodysplastic syndromes), nonmalignant disorders (including severe aplastic anaemia) * Renal injury or inability to tolerate the side effects of CNI: such as CNI renal toxicity (creatinine levels above the upper limit of normal), uncontrolled hypertension, and neurotoxicity rrom the time of hematopoietic stem cell infusion until +90 days after transplantation * Receiving haplo-HSCT for the first time
Exclusion criteria
* Allergy or intolerance to study drugs * Active infection * Active GVHD * Transplantation-associated thrombotic microangiopathy * Key organ dysfunction: liver injury (total bilirubin more than 2 upper limit of normal) or heart injury (symptomatic heart failure or ejection fraction\<50%) * Eastern Cooperative Oncology Group (ECOG) score \>2 * Expected survival time \<30 days * Patients could not cooperate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Grade 2-4 aGVHD within 100 days post transplantation | Participants will be followed for an expected average of 100 days post transplantation |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of chronic GVHD (cGVHD) within 1 year post transplantation | Participants will be followed for an expected average of 1 year |
| Incidence of thrombotic microangiopathy within 1 year post transplantation | Participants will be followed for an expected average of 1 year |
| Cumulative incidence of relapse | Participants will be followed for an expected average of 1 year |
| Transplant-related mortality | Participants will be followed for an expected average of 1 year |
| Overall survival | Participants will be followed for an expected average of 1 year |
| Incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) | Participants will be followed for an expected average of 1 year |
Contacts
CONTACTYuqian Sun
Outcome results
None listed