A Single-arm Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.

Study Overview
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Brief Summary
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A single-arm trial using Tocilizumab for acute GVHD prophylaxis after haploidentical HSCT.

Detailed Description
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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.

Official Title
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A Single-arm, Single-center Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.

Conditions
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Leukemia, Graft-versus-host-disease

Intervention / Treatment
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* Drug: Cytarabine
* Drug: Busulfan
* Drug: Cyclophosphamide
* Drug: Me-CCNU
* Drug: Rabbit antithymocyte globulin
* Drug: Tocilizumab
* Procedure: Allogeneic HSCT
* Drug: Cyclosporin A
* Drug: Mycophenolate Mofetil
* Drug: MTX


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab cohort<br>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<br>* 4 mg/m2/day administered IV day -10 through -9.<br>Drug: Busulfan<br>* 3.2 mg/kg/day administered IV day -8 through -6.<br>Drug: Cyclophosphamide<br>* 1.8 g/m2/day administered IV day -5 through -4.<br>Drug: Me-CCNU<br>* 250mg/m2 once administered orally on day -3.<br>Drug: Rabbit antithymocyte globulin<br>* 1.5mg/kg/day administered IV day -5 through -2.<br>Drug: Tocilizumab<br>* 8mg/kg administered IV on day -1.<br>Procedure: Allogeneic HSCT<br>* Day 0<br>Drug: Cyclosporin A<br>* 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.<br>Drug: Mycophenolate Mofetil<br>* 500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.<br>Drug: MTX<br>* 15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of grade II-IV acute graft-versus-host disease | 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. | 100 days | 
| Cumulative incidence of non grade II-IV acute graft-versus-host disease survival | 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. | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of engraftment | All patients will be tracked from Day 0 to date of myeloid and platelet engraftments, respectively. | 100 days | 
| Cumulative incidence of infections | All patients will be tracked from Day 0 to date of infection diagnosis as proved by relevant standard diagnostic criteria. | 2 years | 
| Overall survival (OS) | 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. | 2 years | 
| Progression-free survival (PFS) | 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. | 2 years | 
| Cumulative incidence of transplant-related nonrelapse mortality (NRM) | 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. | 2 years | 
| Cumulative incidence of disease relapse or progression | 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation, graft-versus-host disease