An Open Label Phase II Pilot Study of Hybrid ImmunoTherapy(ATG/Dexamethasone/Etoposide) for Hemophagocytic LymphoHistiocytosis:HIT-HLH
N/A
18 Years
Both
Hemophagocytic Lymphohistiocytosis
Trial Information
An Open Label Phase II Pilot Study of Hybrid ImmunoTherapy(ATG/Dexamethasone/Etoposide) for Hemophagocytic LymphoHistiocytosis:HIT-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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete Response Rate
Outcome Description:
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
Outcome Time Frame:
8 Weeks
Safety Issue:
Yes
Principal Investigator
Michael Jordan, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Hospital Medical Center, Cincinnati
Authority:
United States: Institutional Review Board
Study ID:
HIT-HLH
NCT ID:
NCT01104025
Start Date:
April 2010
Completion Date:
April 2018
Related Keywords:
- Hemophagocytic Lymphohistiocytosis
- hemophagocytic lymphohistiocytosis
- hybrid immunotherapy
- dexamethasone
- Etoposide
- ATG,rabbit
- Lymphohistiocytosis, Hemophagocytic
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Tulane University Medical Center | New Orleans, Louisiana 70112 |
| Children's Hospital Boston | Boston, Massachusetts 02115 |
| University of California, San Francisco Department of Pediatrics | San Francisco, California |
| Florida All Children's Hospital | St. Petersburg, Florida |
| Texas Children's Cancer Center/Baylor College of Medicine | Houston, Texas |
