Clinical trial NCT06279494: Sirolimus+Abatacept+Mycophenolate Mofetil for Prophylaxis of aGVHD in Patients Receiving Haplo-HSCT Who Are Intolerant to Calcineurin Inhibitors
Official title: Sirolimus+Abatacept+Mycophenolate Mofetil Regimen for Prophylaxis of Acute Graft-versus-host Disease (aGvHD) in Patients Receiving Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HSCT) Who Are Intolerant to Calcineurin Inhibitor
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Leukemia
Myelodysplastic Syndromes
Severe Aplastic Anemia
Keywords: Abatacept
Mycophenolate Mofetil
Sirolimus
Graft-versus-host-disease
Haploidentical
Calcineurin Inhibitor
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 6
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 Abatacept and Mycophenolate Mofetil for the prophylaxis of GVHD in patients with haplo-HSCT who are intolerant to calcineurin inhibitors.


Eligibility criteria: Inclusion criteria:

1. Primary disease: hematological malignancies (including acute leukemia, myelodysplastic syndromes), nonmalignant disorders (including severe aplastic anaemia)
2. Contraindication or intolerance to CNI

   1. Glomerular filtration rate (GFR) 60-89 ml/min/1.73m2 before transplantation or allergy to CNI
   2. Intolerance to CNI during conditioning or within +45 days post transplantation, such as CNI nephrotoxicity (creatinine higher than the upper limit of normal), uncontrolled hypertension, neurological toxicity, or other conditions deemed by physician to be inappropriate for CNI
3. Receiving haplo-HSCT for the first time

Exclusion Criteria:

1. Allergy or intolerance to study drugs
2. Active infection
3. Active GVHD
4. Transplantation-associated thrombotic microangiopathy
5. Key organ dysfunction: liver injury (total bilirubin more than 2 upper limit of normal) or heart injury (symptomatic heart failure or ejection fraction\<50%)
6. Eastern Cooperative Oncology Group (ECOG) score \>2
7. Expected survival time \<30 days
8. Patients could not cooperate

Primary outcomes:
measure: Incidence of Grade 2-4 aGVHD within 100 days post transplantation
timeFrame: Participants will be followed for an expected average of 100 days post transplantation
Secondary outcomes:
measure: Incidence of chronic GVHD (cGVHD) within 1 year post transplantation
timeFrame: Participants will be followed for an expected average of 1 year
measure: Incidence of thrombotic microangiopathy within 1 year post transplantation
timeFrame: Participants will be followed for an expected average of 1 year
Other outcomes:
measure: Cumulative incidence of relapse
timeFrame: Participants will be followed for an expected average of 1 year
measure: Transplant-related mortality
timeFrame: Participants will be followed for an expected average of 1 year
measure: Overall survival
timeFrame: Participants will be followed for an expected average of 1 year
measure: Incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
timeFrame: Participants will be followed for an expected average of 1 year
Locations:
Study officials:
affiliation: Institute of Hematology, Peking University
name: Xiao-Jun Huang
role: PRINCIPAL_INVESTIGATOR
References: