Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis
Condition: Hemophagocytic Lymphohistiocytosis
MeSH terms: Lymphohistiocytosis, Hemophagocytic
Intervention: ATG, rabbit; Etoposide; Methotrexate; hydrocortisone; Dexamethasone
Intervention description: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).; Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.; Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients (CNS+ patients are those patients which have any of the following: elevated CSF (cerebral spinal fluid) protein or white count, seizures, focal or global neurologic deficit, MRI abnormalities consistent with CNS involvement by HLH.) in the following doses: age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg. It will be administered (+/- 3 days) on day 7, 14, 21 and 42.; Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients (CNS+ patients are those patients which have any of the following: elevated CSF (cerebral spinal fluid) protein or white count, seizures, focal or global neurologic deficit, MRI abnormalities consistent with CNS involvement by HLH.) in the following doses: age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg. It will be administered (+/- 3 days) on day 7, 14, 21 and 42.; will be started with the ATG. It will be divided BID, given IV for at least 1 week before switching to PO. Dosing: 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days.
Intervention MeSH terms: Dexamethasone; Hydrocortisone; Methotrexate; Etoposide; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Maximum age: 18 Years
Healthy volunteers: No
Keywords: hemophagocytic lymphohistiocytosis; hybrid immunotherapy; dexamethasone; Etoposide; ATG,rabbit

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.
    

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