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

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

Status

Not yet recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06279494

Enrollment

Registered

2024-02-28

Start date

2024-03-31

Completion date

2025-03-31

Last updated

2024-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Leukemia, Myelodysplastic Syndromes, Severe Aplastic Anemia

Keywords

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

Interventions

DRUGSirolimus

Orally (concentration 5-10ng/ml) from -1 to +100d post haplo-HSCT

DRUGAbatacept

5mg/kg subcutaneous, -1/+5/+14/+28/+42/+56d post haplo-HSCT

DRUGMMF

0.5g bid orally, from -3d to +60d post haplo-HSCT

DRUGATG

2.5 mg/kg, from -5d to -2d

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

14 Years to No maximum

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

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

Other

Measure	Time frame
Incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)	Participants will be followed for an expected average of 1 year
Overall survival	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

Contacts

Primary ContactYuqian Sun, M.D.

sunyuqian83@hotmail.com+86-10-88324577

Backup ContactYuqian Sun