Clinical trial NCT01104025: Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis
Official title: An Open Label Phase II Pilot Study of Hybrid ImmunoTherapy(ATG/Dexamethasone/Etoposide) for Hemophagocytic LymphoHistiocytosis:HIT-HLH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophagocytic Lymphohistiocytosis
Keywords: hemophagocytic lymphohistiocytosis
hybrid immunotherapy
dexamethasone
Etoposide
ATG,rabbit
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2010-04-15
Enrollment: 31
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 8 Weeks
Secondary outcomes:
measure: Time to Response
timeFrame: 8 Weeks
measure: Overall Survival
timeFrame: up to day 180
measure: Number of Participants Who Experienced Reactivation
timeFrame: up to 180 days
measure: Overall Survival to Day +100
timeFrame: up to day 280
measure: Disease Status at BMT
timeFrame: up to day 180
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: San Francisco
country: United States
facility: University of California, San Francisco Department of Pediatrics
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Nemours
state: Florida
city: Saint Petersburg
country: United States
facility: Florida All Children's Hospital
state: Florida
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Cancer Center/Baylor College of Medicine
state: Texas
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Michael Jordan, MD
role: PRINCIPAL_INVESTIGATOR
References: