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

NCT06279494 | Not Yet Recruiting Phase 1

• 1 other identifier: Sirolimus for GVHD prophylaxis
• Study Type: interventional
• Target: 6
• 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 Abatacept 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

Keywords

Abatacept; Mycophenolate Mofetil; Sirolimus; 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 (2)

• 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 Outcomes (4)

• 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+Abatacept+Mycophenolate mofetil (MMF)+anti-thymocyte globulin (ATG)

EXPERIMENTAL

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

Drug: Sirolimus; Drug: Abatacept; Drug: MMF; Drug: ATG

Interventions

Sirolimus DRUG

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

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

Abatacept DRUG

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

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

MMF DRUG

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

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

ATG DRUG

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

Sirolimus+Abatacept+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)
• Contraindication or intolerance to CNI
• Glomerular filtration rate (GFR) 60-89 ml/min/1.73m2 before transplantation or allergy to CNI
• 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
• 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; Abatacept

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; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Xiao-Jun Huang

  Institute of Hematology, Peking University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuqian Sun, M.D.

CONTACT

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

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: Prof.

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: February 28, 2024
• Study Start: March 1, 2024
• Primary Completion: June 1, 2024
• Study Completion: March 1, 2025
• Last Updated: March 21, 2024

Record last verified: 2024-03