Sirolimus+Ruxolitinib+Mycophenolate Mofetil for Prophylaxis of aGVHD in Patients Receiving Haplo-HSCT Who Are Intolerant to CNI

Sirolimus+Ruxolitinib+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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Myelodysplastic Syndromes; Acute Leukemia; Severe Aplastic Anemia (SAA)
• Intervention / Treatment: Drug: ATG; Drug: Sirolimus; Drug: Ruxolitinib; Drug: MMF

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yuqian Sun; Phone Number: +86-10-88324577; Email: sunyuqian83@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sirolimus+Ruxolitinib+Mycophenolate mofetil (MMF)+anti-thymocyte globulin (ATG); Patients receiving haplo-HSCT who are intolerant to calcineurin inhibitors would receive Sirolimus+Ruxolitinib+MMF+ATG (SRMA) for prophylaxis of aGVHD

Drug: ATG; 2.5 mg/kg, from -5d to -2d; Drug: Sirolimus; 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.; Drug: Ruxolitinib; 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.; Drug: MMF; 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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: August 27, 2026
• First Submitted That Met QC Criteria: August 27, 2026
• First Posted (Actual): September 1, 2026

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Ruxolitinib; Mycophenolate Mofetil; Sirolimus; Haploidentical; Graft-versus-host-disease; Calcineurin Inhibitor
• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Immune System Diseases; Hematologic Diseases; Bone Marrow Diseases; Anemia; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Anemia, Aplastic; Graft vs Host Disease; Organic Chemicals; Macrolides; Lactones; Sirolimus; ruxolitinib
• Other Study ID Numbers: Sirolimus for GVHD prevention

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No