Clinical trial NCT03533101: Tocilizumab for Cytokine Release Syndrome Prophylaxis in Haploidentical Transplantation
Official title: Tocilizumab for Cytokine Release Syndrome Prophylaxis in Peripheral Blood Haploidentical Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cytokine Release Syndrome
Stem Cell Transplant Complications
Keywords: Tocilizumab
Haploidentical
Peripheral blood
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2018-05-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Adaptive design using two different doses of tocilizumab prophylaxis
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cytokine release syndrome
timeFrame: 1 week
Secondary outcomes:
measure: Hospitalization rate
timeFrame: 1 week
measure: Adverse effects
timeFrame: 1 week
measure: IL-6 concentration
timeFrame: 1 week
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose E Gonzalez UANL
state: Nuevo Leon
Study officials:
affiliation: Hospital Universitario "Dr. José Eleuterio González"
name: David Gómez-Almaguer, MD
role: STUDY_DIRECTOR
References:
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.
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. No abstract available.
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.
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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 KPA, Tey SK, Hill GR. Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol. 2014 Dec;15(13):1451-1459. doi: 10.1016/S1470-2045(14)71017-4. Epub 2014 Nov 14.
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 of acute graft-versus-host disease: low incidence of lower gastrointestinal tract disease. Haematologica. 2018 Apr;103(4):717-727. doi: 10.3324/haematol.2017.183434. Epub 2018 Jan 19.