We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01104025
First Posted: April 15, 2010
Last Update Posted: November 16, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
April 13, 2010
April 15, 2010
November 16, 2016
April 2010
November 2015   (Final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01104025 on ClinicalTrials.gov Archive Site
  • 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
  • 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
Not Provided
Not Provided
 
Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis
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).
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hemophagocytic Lymphohistiocytosis
  • Drug: ATG, rabbit
    ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
    Other Name: Thymoglobulin
  • Drug: Etoposide
    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.
    Other Names:
    • Etopophos
    • Toposar
    • VePesid
  • Drug: Methotrexate
    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.
  • Drug: hydrocortisone
    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.
  • Drug: Dexamethasone
    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.
Experimental: Induction Therapy
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg, on day 7, 14, 21 and 42
Interventions:
  • Drug: ATG, rabbit
  • Drug: Etoposide
  • Drug: Methotrexate
  • Drug: hydrocortisone
  • Drug: Dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
April 2016
November 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 18 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT01104025
HIT-HLH
Yes
Not Provided
Not Provided
Children's Hospital Medical Center, Cincinnati
Children's Hospital Medical Center, Cincinnati
Not Provided
Principal Investigator: Michael Jordan, MD Children's Hospital Medical Center, Cincinnati
Children's Hospital Medical Center, Cincinnati
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP