Sirolimus+Abatacept+Mycophenolate Mofetil for Prophylaxis of aGVHD in Patients Receiving Haplo-HSCT Who Are Intolerant to Calcineurin Inhibitors

Peking University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Acute Leukemia; Myelodysplastic Syndromes; Severe Aplastic Anemia

Treatments: Drug: ATG; Drug: Abatacept; Drug: MMF; Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT06279494

Sirolimus for GVHD prophylaxis

Details and patient eligibility

About

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.

Enrollment: 6 estimated patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Sirolimus+Abatacept+Mycophenolate mofetil (MMF)+anti-thymocyte globulin (ATG)

Experimental group

Description:

Patients receiving haplo-HSCT who are intolerant to calcineurin inhibitors would receive Sirolimus+Abatacept+MMF+ATG (SAMA) for prophylaxis of aGVHD

Treatment:

Drug: ATG

Drug: MMF

Drug: Sirolimus

Drug: Abatacept