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

March 19, 2024 updated by: Xiao-Jun Huang, Peking University People's Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sirolimus+Abatacept+Mycophenolate mofetil (MMF)+anti-thymocyte globulin (ATG)
Patients receiving haplo-HSCT who are intolerant to calcineurin inhibitors would receive Sirolimus+Abatacept+MMF+ATG (SAMA) for prophylaxis of aGVHD
Drug: Sirolimus
Orally (concentration 5-10ng/ml) from -1 to +100d post haplo-HSCT
Drug: Abatacept
5mg/kg subcutaneous, -1/+5/+14/+28/+42/+56d post haplo-HSCT
Drug: MMF
0.5g bid orally, from -3d to +60d post haplo-HSCT
Drug: ATG
2.5 mg/kg, from -5d to -2d

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Grade 2-4 aGVHD within 100 days post transplantation
Time Frame: Participants will be followed for an expected average of 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
Time Frame: Participants will be followed for an expected average of 1 year
Participants will be followed for an expected average of 1 year
Incidence of thrombotic microangiopathy within 1 year post transplantation
Time Frame: Participants will be followed for an expected average of 1 year
Participants will be followed for an expected average of 1 year

Other Outcome Measures

Outcome Measure
Time Frame
Cumulative incidence of relapse
Time Frame: Participants will be followed for an expected average of 1 year
Participants will be followed for an expected average of 1 year
Transplant-related mortality
Time Frame: Participants will be followed for an expected average of 1 year
Participants will be followed for an expected average of 1 year
Overall survival
Time Frame: Participants will be followed for an expected average of 1 year
Participants will be followed for an expected average of 1 year
Incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
Time Frame: Participants will be followed for an expected average of 1 year
Participants will be followed for an expected average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Investigators

  • Principal Investigator: Xiao-Jun Huang, Institute of Hematology, Peking University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

February 9, 2024

First Submitted That Met QC Criteria

February 25, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sirolimus for GVHD prophylaxis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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