Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Azienda Ospedaliero, Universitaria Meyer
Leiden University Medical Center
Children's Hospital Medical Center, Cincinnati
Ehime University Graduate School of Medicine
Universitätsklinikum Hamburg-Eppendorf
Texas Children's Hospital
Great Ormond Street Hospital for Children NHS Foundation Trust
St. Anna Kinderkrebsforschung
Hospital de Cruces
Hospital JP Garrahan
Information provided by (Responsible Party):
Jan-Inge Henter, Karolinska University Hospital
ClinicalTrials.gov Identifier:
NCT00426101
First received: January 23, 2007
Last updated: November 22, 2012
Last verified: November 2012

January 23, 2007
November 22, 2012
January 2004
December 2011   (final data collection date for primary outcome measure)
Survival [ Time Frame: 1-year after diagnosis ] [ Designated as safety issue: No ]
Survival
Complete list of historical versions of study NCT00426101 on ClinicalTrials.gov Archive Site
Late effects [ Time Frame: At last follow-up report ] [ Designated as safety issue: No ]
Late effects
Not Provided
Not Provided
 
Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004
HLH-2004 Treatment Protocol

Without therapy HLH is often fatal, and often rapidly fatal. The treatment protocol HLH-94 has improved survival markedly as compared to the survival earlier. We now aim to improve survival further.

The most dangerous period after HLH diagnosis is the first 2 months. In HLH-2004 we provide additional therapy during this period as compared to in HLH-94.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophagocytic Lymphohistiocytosis
  • Drug: Dexamethasone
    • Dexamethasone 10 mg/m2 daily, for the first 2 weeks (week 1-2).
    • Dexamethasone 5 mg/m2 daily, for another 2 weeks (week 3-4).
    • Dexamethasone 2.5 mg/m2 daily, for another 2 weeks (week 5-6)
    • Dexamethasone 1.25 mg/m2 daily, for another week (week 7). Steroids are tapered and discontinued during week 8.

    If continuation therapy is provided, then:

    - Dexamethasone pulses every second week, 10 mg/m2 for 3 days.

  • Drug: Etoposide
    • 150 mg/m2 iv twice weekly (week 1-2).
    • 150 mg/m2 iv once weekly (week 3-8).

    If continuation therapy is provided, then:

    - 150 mg/m2 iv, every second week.

  • Drug: Cyclosporin

    WEEK 1-8:

    - The blood levels determine the dosages, aim at levels around 200 microgram/L (trough value) (monoclonal antibody assay of whole blood). Start with 6 mg/kg daily (divided in 2 daily doses) already week 1, if kidney function is normal.

    If continuation therapy is provided, then:

    - Aim for blood levels around 200 microgram/L, as above. Monitor GFR.

  • Procedure: Intrathecal therapy

    The CSF is evaluated at diagnosis and after 2 weeks. If after 2 weeks there is clinical evidence of progressive neurological symptoms or if an abnormal CSF (cell count and protein) has not improved, additional CNS-therapy is initiated with 4 weekly intrathecal injections. Be aware that some patients may have increased intracranial pressure.

    • Methotrexate: <1 yr 6 mg, 1-2 yrs 8 mg, 2-3 yrs 10 mg, >3 yrs 12 mg.
    • Prednisolone: <1 yr 4 mg, 1-2 yrs 6 mg, 2-3 yrs 8 mg, >3 yrs 10 mg.
  • Procedure: Stem cell transplant

    Suggested regimen:

    Preparative Regimen

    • Day -8,-7,-6,-5 Busulfan 2mg/kg po, or eq iv (as 1.6mg/kg), twice daily.
    • Day -4 Etoposide 30 mg/kg iv (6 hr inf) (maximum 1800 mg)
    • Day -3, -2 Cyclophosphamide 60 mg/kg iv (1 hr inf)
    • Day 0 Marrow infusion (preferably ³3 x 108 nucleated cells/kg, non T-cell-depleted).

    GVHD Prophylaxis:

    1. CSA continuous infusion starting day -1 pre-transplant with 3 mg/kg until oral nutrition re-established, thereafter 12.5 mg/kg orally daily. Monitoring of CSA through concentration levels. The immunosuppression is discontinued after 6-12 months, if possible.
    2. Short course methotrexate:

      • Day +1 15 mg/m2 iv
      • Day +3 10 mg/m2 iv
      • Day +6 10 mg/m2 iv Methotrexate may be substituted by mycophenolate mofetil (MMF).

    Additional Treatment for URD

    • ATG (12 hr inf iv) on days -3, -2 and -1 (according to manufacturers rec).
    • Metronidazole 22 mg/kg daily (po or iv) from day -8 until discharge.
Not Provided
Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
300
December 2016
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients who fulfil the diagnostic criteria of HLH.

Exclusion Criteria:

  • Prior cytotoxic or cyclosporin treatment for HLH.
Both
up to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
Sweden
 
NCT00426101
HLH-2004
Yes
Jan-Inge Henter, Karolinska University Hospital
Karolinska University Hospital
  • Azienda Ospedaliero, Universitaria Meyer
  • Leiden University Medical Center
  • Children's Hospital Medical Center, Cincinnati
  • Ehime University Graduate School of Medicine
  • Universitätsklinikum Hamburg-Eppendorf
  • Texas Children's Hospital
  • Great Ormond Street Hospital for Children NHS Foundation Trust
  • St. Anna Kinderkrebsforschung
  • Hospital de Cruces
  • Hospital JP Garrahan
Principal Investigator: Jan-Inge Henter, MD, PhD Karolinska Institutet
Karolinska University Hospital
November 2012

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