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

NCT07796620 | Not Yet Recruiting Phase 1

• 1 other identifier: Sirolimus for GVHD prevention
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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

Conditions

Acute Leukemia; Myelodysplastic Syndromes; Severe Aplastic Anemia (SAA)

Keywords

Ruxolitinib; Sirolimus; Mycophenolate Mofetil; Graft-versus-host-disease; Haploidentical; Calcineurin Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (1)

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

EXPERIMENTAL

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

Drug: Sirolimus; Drug: Ruxolitinib; Drug: MMF; Drug: ATG

Interventions

Sirolimus DRUG

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.

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

Ruxolitinib DRUG

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.

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

MMF DRUG

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.

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

ATG DRUG

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

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

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University People's Hospital: lead

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Aplastic; Graft vs Host Disease

Interventions

Sirolimus; ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Bone Marrow Failure Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Yuqian Sun

CONTACT

+86-10-88324577; sunyuqian83@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of the Department of Hematology

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 1, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: September 9, 2026

Record last verified: 2026-09