Tocilizumab for Cytokine Release Syndrome Prophylaxis in Haploidentical Transplantation

Phase 1

Completed

• Conditions: Stem Cell Transplant Complications; Cytokine Release Syndrome
• Interventions: Drug: Tocilizumab

• Registration Number: NCT03533101
• Lead Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-05-10
• Study First Submitted QC: 2018-05-21
• Study First Posted: 2018-05-22
• Study Start: 2018-05-25
• Primary Completion: 2019-05-15
• Study Completion: 2019-06-15
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-05
• Last Update Posted: 2021-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tocilizumab 4 mg/kg	Tocilizumab	Tocilizumab 4 mg/kg IV single dose day -1 prior to haploidentical transplantation
Tocilizumab 8 mg/kg	Tocilizumab	Tocilizumab 8 mg/kg IV single dose day -1 prior to haploidentical transplantation

Primary Outcome Measures

Name	Time	Method
Cytokine release syndrome	1 week	Incidence of fever in the first seven days after haploidentical transplantation

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hospital Universitario Dr. Jose E Gonzalez UANL; 🇲🇽 Monterrey, Nuevo Leon, Mexico