Clinical Trial: Tocilizumab and Hemophagocytic Lymphohistiocytosis (HLH)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Cytokine Blockade With Tocilizumab in Patients With Cytokine Release Syndrome and Hemophagocytic Lymphohistiocytosis

Brief Summary: This study seeks to determine the efficacy of tocilizumab (TCZ) in patients with hemophagocytic lymphohistiocytosis (HLH) and high cytokine levels (proteins involved in inflammation) in an attempt to decrease the damage caused by these proteins; and secondarily to assess its safety and impact on disease activity.

Detailed Summary:

Subjects with hemophagocytic lymphohistiocytosis (HLH) often have life-threatening complications at the time of diagnosis resulting from excessive inflammation. This excessive inflammation is driven by abnormally high levels of cytokines--proteins involved in inflammation. Standard therapy for HLH does not directly target these cytokines. Tocilizumab is a medicine that blocks one of the cytokines that is elevated in patients with HLH.

This is an open-label single-arm uncontrolled trial with biologic endpoint. This study will use tocilizumab in subjects with HLH and high cytokine levels in an attempt to decrease the damage caused by these proteins. All subjects will receive standard therapy, in addition to tocilizumab. We hypothesize the tocilizumab will decrease levels of certain important cytokines. This may make it easier to treat subjects with HLH overall.

TCZ will be administered as a single dose (8mg/kg) intravenously. Eligible subjects will be inpatients at the Children's Hospital of Philadelphia (CHOP) main campus. 10 subjects with HLH will be enrolled. All subjects will be initiated on standard HLH-directed treatment. Cytokine levels [including serum interferon (IFN-γ) and interleukin (IL-6)] will be monitored, in addition to other laboratory and clinical markers of HLH disease activity.


Sponsor: Children's Hospital of Philadelphia

Current Primary Outcome: Reduction in serum interferon-gamma levels after tocilizumab (TCZ) administration [ Time Frame: baseline, 24 -36 hours, and 4-7 days after administration of TCZ ]

Assess change in interferon gamma levels from the screening visit to the measurements taken within 24-36 hours and at 4-7 days after drug administration.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in other cytokine levels (interleukin-6, interleukin-10, tumor necrosis factor-alpha, etc.) [ Time Frame: baseline, 24-36 hour, then weekly for 4 weeks after administration of TCZ ]
    Cytokine levels [IL-1, IL-2, sIL-2r, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, Tumor necrosis factor-alpha (TNF-α) and IFN-γ] will be assessed at baseline, within 24-36 hours, then weekly for 4 weeks after TCZ administration;
  • Presence of HLH disease activity for each subject following TCZ administration [ Time Frame: within 1 week of administration of TCZ ]
    HLH disease activity markers will be assessed for each subject (fever, ferritin, cardiopulmonary support requirements, cytopenias, coagulation tests, etc.)
  • Degree of hepatic function, cytopenias and infection in subjects following administration of TCZ [ Time Frame: up to 1 year of administration of TCZ ]
    Degree of hepatic function, presence (or absence) of cytopenia/infection will be assessed based on changes in laboratory and clinical markers following administration of TCZ.
  • Overall survival of subjects [ Time Frame: day 100 and survival to completion of therapy (blood/marrow transplant, if applicable) ]
    Overall survival of subjects will include survival to day 100, and survival to completion of therapy (HSCT for primary HLH, and end of induction therapy for secondary HLH).


Original Secondary Outcome: Same as current

Information By: Children's Hospital of Philadelphia

Dates:
Date Received: December 5, 2013
Date Started: December 2013
Date Completion: July 2018
Last Updated: February 15, 2017
Last Verified: February 2017