Tocilizumab for Cytokine Release Syndrome Prophylaxis in Haploidentical Transplantation

Study Overview
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Brief Summary
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Tocilizumab will be administered prior to transplantation in order to prevent the onset of cytokine release syndrome and its complications associated to peripheral blood haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide

Detailed Description
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Cytokine release syndrome (CRS) is a common and potentially severe toxicity associated to haploidentical peripheral blood (PBSC) hematopoietic stem cell transplantation (Haplo-HSCT), which was described previously in the context of immunotherapies for acute lymphoblastic leukemia such as chimeric antigen receptor T-cells and blinatumomab. CRS is characterized by immune system activation with a high level of circulating inflammatory cytokines including IL-6. Haplo-HSCT recipients have a high incidence of post-transplant fever, with elevated IL-6 in absence of documented infection. CRS occurs more frequently when using PBSC, and severe cases have been associated to delayed engraftment, increased transplant-related mortality and lower survival. Tocilizumab an IL-6 receptor-targeted monoclonal antibody has been effectively used to treat CRS in several scenarios, including Haplo-HSCT. Therefore, there is considerable interest for the development of a successful strategy for CRS prevention with tocilizumab, potentially eliminating complications. However, it is currently unknown whether the use of this monoclonal antibody can adversely affect the outcome of Haplo-HSCT recipients.

Official Title
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Tocilizumab for Cytokine Release Syndrome Prophylaxis in Peripheral Blood Haploidentical Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide

Conditions
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Cytokine Release Syndrome, Stem Cell Transplant Complications

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Haploidentical transplant recipients Informed consent signature Previous diagnosis of any neoplastic, metabolic or autoimmune disease Exclusion Criteria: History of immune deficiency virus infection Hepatitis C or B virus infection Documented bacterial of fungal infection prior to tocilizumab infusion Previous use of tocilizumab

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Adaptive design using two different doses of tocilizumab prophylaxis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab 4 mg/kg<br>Tocilizumab 4 mg/kg IV single dose day -1 prior to haploidentical transplantation | Drug: Tocilizumab<br>* IL-6 receptor antibody pre-transplant administration to avoid cytokine release syndrome<br>* Other names: RoActemra;|
| Active Comparator: Tocilizumab 8 mg/kg<br>Tocilizumab 8 mg/kg IV single dose day -1 prior to haploidentical transplantation | Drug: Tocilizumab<br>* IL-6 receptor antibody pre-transplant administration to avoid cytokine release syndrome<br>* Other names: RoActemra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine release syndrome | Incidence of fever in the first seven days after haploidentical transplantation | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization rate | Incidence of hospitalization in the first seven days after haploidentical transplantation | 1 week | 
| Adverse effects | According to Common Terminology Criteria for Adverse Events v5.0 | 1 week | 
| IL-6 concentration | Concentration of serum IL-6 prior and during the first week after transplantation| | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tocilizumab, Haploidentical, Peripheral blood