Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis

Status:	Completed
Conditions:	Hematology
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	Any - 18
Updated:	6/11/2016
Start Date:	April 2010
End Date:	April 2016

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

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.

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).

Inclusion Criteria:

- diagnosis of hemophagocytic lymphohistiocytosis

- Patients <18 years of age

- The patient must have active disease at the time of enrollment

- Patient's legal guardians must sign an Institutional Review Board approved consent
form indicating their awareness of the investigational nature and the risks of this
study.

- Eligible subjects must be enrolled with the protocol coordinating center

Exclusion Criteria:

- Recent treatment, within 3 months, with another therapeutic regimen for HLH

- Known active malignancy

- Known rheumatologic diagnosis which may be the underlying cause of HLH

- Pregnancy (as determined by serum or urine test) or active breast feeding

- Failure to provide signed informed consent

We found this trial at

sites

Childrens National Medical Center

111 Michigan Ave NW
Washington, District of Columbia

(202) 476-5000