Tocilizumab for Cytokine Release Syndrome Prophylaxis in Haploidentical Transplantation

Stem Cell Transplant Complications Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03533101
• Other study ID #: HE18-00010
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 25, 2018
• Est. completion date: June 15, 2019

Study information

• Verified date: March 2021
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 15, 2019
• Est. primary completion date: May 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cytokine Release Syndrome
• Stem Cell Transplant Complications
• Syndrome

Intervention

Drug:
• Tocilizumab
IL-6 receptor antibody pre-transplant administration to avoid cytokine release syndrome

Locations

Country	Name	City	State
Mexico	Hospital Universitario Dr. Jose E Gonzalez UANL	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (6)

Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, Meier S, Fehniger TA, Abboud CN, Uy GL, Vij R, Trinkaus KM, Schroeder MA, Romee R. Severe Cytokine-Release Syndrome after T Cell-Replete Peripheral Blood Haploidentical Donor Transplantati — View Citation

Drobyski WR, Szabo A, Zhu F, Keever-Taylor C, Hebert KM, Dunn R, Yim S, Johnson B, D'Souza A, Eapen M, Fenske TS, Hari P, Hamadani M, Horowitz MM, Rizzo JD, Saber W, Shah N, Shaw B, Pasquini M. Tocilizumab, tacrolimus and methotrexate for the prevention o — View Citation

Kennedy GA, Varelias A, Vuckovic S, Le Texier L, Gartlan KH, Zhang P, Thomas G, Anderson L, Boyle G, Cloonan N, Leach J, Sturgeon E, Avery J, Olver SD, Lor M, Misra AK, Hutchins C, Morton AJ, Durrant ST, Subramoniapillai E, Butler JP, Curley CI, MacDonald — View Citation

Raj RV, Hamadani M, Szabo A, Pasquini MC, Shah NN, Drobyski WR, Shaw BE, Saber W, Rizzo JD, Jerkins J, Fenske TS, D'Souza A, Dhakal B, Zhang C, Konings S, Hari PN, Chhabra S. Peripheral Blood Grafts for T Cell-Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome. Biol Blood Marrow Transplant. 2018 Aug;24(8):1664-1670. doi: 10.1016/j.bbmt.2018.04.010. Epub 2018 Apr 19. — View Citation

Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016 Jul;8(8):959-70. doi: 10.2217/imt-2016-0020. Review. — View Citation

Teachey DT, Grupp SA. Cytokine Release Syndrome after Haploidentical Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016 Oct;22(10):1736-1737. doi: 10.1016/j.bbmt.2016.08.010. Epub 2016 Aug 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cytokine release syndrome	Incidence of fever in the first seven days after haploidentical transplantation	1 week
Secondary	Hospitalization rate	Incidence of hospitalization in the first seven days after haploidentical transplantation	1 week
Secondary	Adverse effects	According to Common Terminology Criteria for Adverse Events v5.0	1 week
Secondary	IL-6 concentration	Concentration of serum IL-6 prior and during the first week after transplantation|	1 week