A Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.
- Conditions
- LeukemiaGraft-versus-host-disease
- Interventions
- Registration Number
- NCT04688021
- Lead Sponsor
- Yi Luo
- Brief Summary
A single-arm trial using Tocilizumab for acute GVHD prophylaxis after haploidentical HSCT.
- Detailed Description
This study will enroll haploidentical HSCT patients with high risk for acute GVHD. Tocilizumab (8mg/kg) will be added to the conventional acute GVHD prophylaxis regime (CsA+Methotrexate(MTX)+low dose mycophenolate mofetil(MMF)+ATG) on day -1 of transplant. The previous patients will be used as control.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 46
- Patients with hematological malignancies in complete remission (CR) who are eligible and planned for haploidentical HSCT. The donor specific antibody is negative
- Patient age 16-60 years
- Mother donor, or female donor (age >50) for female-male transplant
- Eastern Cooperative Oncology Group (ECOG) performance status < 2
- Creatinine clearance rate > 60 mL/min (estimate by Cockcroft-Gault Equation)
- alanine transaminase (ALT) and aspartate aminotransferase (AST)≤ 2.5×upper limit of normal (ULN), and total bilirubin ≤ 1.5×ULN （upper limit of normal, ULN）
- Left ventricular ejection fraction (LVEF) ≥50% as measured by echocardiography
- Acceptation to sign the informed consent
- History of previous HSCT
- Present active infection (including bacterial, virus or fungal)
- History of Tocilizumab infection
- History of inflammatory bowel disease
- History of demyelinating disease
- Patients who are HIV-positive, or with uncontrolled chronic hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV) infections
- Women who are pregnant (β-chorionic gonadotropin+) or breast feeding
- Refusal to sign the informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tocilizumab cohort Me-CCNU Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Allogeneic HSCT Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Cytarabine Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Busulfan Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Rabbit antithymocyte globulin Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Cyclophosphamide Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Tocilizumab Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Cyclosporin A Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort Mycophenolate Mofetil Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT. Tocilizumab cohort MTX Each patient receives Tocilizumab (8 mg/kg, i.v.) on day -1 added to conventional acute GVHD prophylaxis regimen (CsA+MTX+low-dose MMF+ATG) of haploidentical HSCT.
- Primary Outcome Measures
Name Time Method Cumulative incidence of grade II-IV acute graft-versus-host disease 100 days Date of symptom onset, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II-IV acute graft-versus-host disease (aGVHD) will be recorded. The aGVHD score of each affected organ will be recorded.
Cumulative incidence of non grade II-IV acute graft-versus-host disease survival 100 days All patients will be tracked from Day 0 to date of grade II-IV acute graft-versus-host disease (aGVHD) onset. Patients who did not present grade II-IV aGVHD or died will be censored at the last date they were assessed and deemed free of grade II-IV aGVHD.
- Secondary Outcome Measures
Name Time Method Cumulative incidence of engraftment 100 days All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively.
Cumulative incidence of infections 2 years All patients will be tracked from Day 0 to date of infection diagnosis as proved by relevant standard diagnostic criteria.
Overall survival (OS) 2 years All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Progression-free survival (PFS) 2 years All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Cumulative incidence of transplant-related nonrelapse mortality (NRM) 2 years All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Cumulative incidence of disease relapse or progression 2 years All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Trial Locations
- Locations (1)
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳Hangzhou, China