Clinical Trial: Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label Phase II Pilot Study of Hybrid ImmunoTherapy(ATG/Dexamethasone/Etoposide) for Hemophagocytic LymphoHistiocytosis:HIT-HLH

Brief Summary:

Despite good progress during the last decade, hemophagocytic lymphohistiocytosis (HLH) remains difficult to treat. Two different treatment regimens have been used successfully. The first one, a treatment regimen based on two drugs called etoposide and dexamethasone, has been used worldwide. The second regimen, based on two drugs called Anti-thymocyte globulin (ATG) and prednisone, has been used mostly at one hospital in Paris, for over 15 years. With either regimen, about three quarters of treated children survive the most difficult time, the first two months after diagnosis. These two different regimens appear to work somewhat differently, and we suspect that combining them may give better results than either regimen alone. We are conducting this clinical trial to test the combination of ATG, dexamethasone, and etoposide for the treatment of HLH.

The purpose of this research study is to find out what effects (good and bad) this drug combination has on you and your HLH.


Detailed Summary: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder first recognized almost 70 years ago.(1) Genetic and animal studies have indicated that the familial form of HLH is clearly due to a deficiency of cytotoxic killing. Patients with HLH present with a potentially fatal syndrome of 'hyperimmunity.' These patients have severe inflammation, associated with cytopenias and variably severe bone marrow, liver, or CNS damage. Tissue damage and mortality appear to be due to hypercytokinemia related to persistent immune hyperactivation. An animal model of HLH and correlative human studies all suggest that excessive and abnormal activation of T cells drives the pathophysiology of this disorder, and that suppressing this excessive activation is critical for successful therapy of HLH. It is believed a combination of the two proven induction regimens for hemophagocytic lymphohistiocytosis (HLH) (anti-thymocyte globulin (ATG)- and etoposide-based) will result in response rates and overall survival rates at eight weeks which are comparable or better than the current standard of care (induction therapy per the HLH-94 protocol).
Sponsor: Children's Hospital Medical Center, Cincinnati

Current Primary Outcome: Complete Response Rate [ Time Frame: 8 Weeks ]

To determine the complete response rate and overall survival at 8 weeks after an ATG/Dexamethasone/Etoposide based induction regimen for patients with hemophagocytic lymphohistiocytosis


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to Response [ Time Frame: 8 Weeks ]
    To determine the median time to complete response
  • Overall Survival [ Time Frame: 8 weeks ]
    To determine overall survival prior to the initiation of BMT (bone marrow transplant) preparative regimen (or day 180, if BMT preparative regimen not yet begun)
  • Incidence of Infection [ Time Frame: 8 Weeks or day 180 ]
    To determine the incidence of serious infection and other adverse events by week 8 and prior to initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)
  • Incidence and Time to Relapse [ Time Frame: 8 weeks ]
    To determine the incidence and median time to relapse prior to initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)
  • Overall Survival to day +100 [ Time Frame: 8 weeks ]
    To determine overall survival to day +100 after BMT, for patients who have undergone BMT within 6 months of study entry
  • Gather Biologic Samples [ Time Frame: 8 weeks ]
    To gather biologic samples from patients with HLH to facilitate future basic and translational studies


Original Secondary Outcome:

  • Time to Response [ Time Frame: 8 Weeks ]
    To determine the median time to complete response
  • Overall Survival [ Time Frame: 8 weeks ]
    To determine overall survival prior to the initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)
  • Incidence of Infection [ Time Frame: 8 Weeks or day 180 ]
    To determine the incidence of serious infection and other adverse events by week 8 and prior to initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)
  • Incidence and Time to Relapse [ Time Frame: 8 weeks ]
    To determine the incidence and median time to relapse prior to initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)
  • Overall Survival to day +100 [ Time Frame: 8 weeks ]
    To determine overall survival to day +100 after BMT, for patients who have undergone BMT within 6 months of study entry
  • Gather Biologic Samples [ Time Frame: 8 weeks ]
    To gather biologic samples from patients with HLH to facilitate future basic and translational studies


Information By: Children's Hospital Medical Center, Cincinnati

Dates:
Date Received: April 13, 2010
Date Started: April 2010
Date Completion:
Last Updated: November 15, 2016
Last Verified: November 2016