A Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.
Study Details
Study Description
Brief Summary
A single-arm trial using Tocilizumab for acute GVHD prophylaxis after haploidentical HSCT.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tocilizumab cohort 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. |
Drug: Cytarabine
4 mg/m2/day administered IV day -10 through -9.
Drug: Busulfan
3.2 mg/kg/day administered IV day -8 through -6.
Drug: Cyclophosphamide
1.8 g/m2/day administered IV day -5 through -4.
Drug: Me-CCNU
250mg/m2 once administered orally on day -3.
Drug: Rabbit antithymocyte globulin
1.5mg/kg/day administered IV day -5 through -2.
Drug: Tocilizumab
8mg/kg administered IV on day -1.
Procedure: Allogeneic HSCT
Day 0
Drug: Cyclosporin A
2.5 mg/kg/day administered intravenously from day -7, target: 200-300ng/mL. Usually tapered during the second month, and ended in complete withdrawal during the ninth month after transplantation.
Drug: Mycophenolate Mofetil
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
Drug: MTX
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital, College of Medicine, Zhejiang University | Hangzhou | China |
Sponsors and Collaborators
- Yi Luo
Investigators
- Principal Investigator: Yi Luo, First Affiliated Hospital of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TZ-001