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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06279494
• Other study ID #: Sirolimus for GVHD prophylaxis
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2024
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Peking University People's Hospital
• Contact: Yuqian Sun, M.D.
• Phone: +86-10-88324577
• Email: sunyuqian83[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: March 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia
• Anemia, Aplastic
• Myelodysplastic Syndromes
• Severe Aplastic Anemia

Intervention

Drug:
• Sirolimus
Orally (concentration 5-10ng/ml) from -1 to +100d post haplo-HSCT
• Abatacept
5mg/kg subcutaneous, -1/+5/+14/+28/+42/+56d post haplo-HSCT
• MMF
0.5g bid orally, from -3d to +60d post haplo-HSCT
• ATG
2.5 mg/kg, from -5d to -2d

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cumulative incidence of relapse		Participants will be followed for an expected average of 1 year
Other	Transplant-related mortality		Participants will be followed for an expected average of 1 year
Other	Overall survival		Participants will be followed for an expected average of 1 year
Other	Incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)		Participants will be followed for an expected average of 1 year
Primary	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	Incidence of chronic GVHD (cGVHD) within 1 year post transplantation		Participants will be followed for an expected average of 1 year
Secondary	Incidence of thrombotic microangiopathy within 1 year post transplantation		Participants will be followed for an expected average of 1 year