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Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

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ClinicalTrials.gov Identifier: NCT00426101
Recruitment Status : Active, not recruiting
First Posted : January 24, 2007
Last Update Posted : March 14, 2017
Information provided by (Responsible Party):

January 23, 2007
January 24, 2007
March 14, 2017
January 2004
December 2011   (Final data collection date for primary outcome measure)
Survival [ Time Frame: 1-year after diagnosis ]
Complete list of historical versions of study NCT00426101 on ClinicalTrials.gov Archive Site
Late effects [ Time Frame: 5-years after diagnosis ]
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.
Phase 3
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hemophagocytic Lymphohistiocytosis
  • Drug: Dexamethasone

    10 mg/m2 daily wk 1-2 5 mg/m2 daily wk 3-4 2.5 mg/m2 daily wk 5-6 1.25 mg/m2 daily wk 7 Steroids tapered wk 8

    If continuation:

    Pulses every 2nd wk, 10 mg/m2 for 3 days

  • Drug: Etoposide

    150 mg/m2 iv twice/wk (wk 1-2) 150 mg/m2 iv once/wk (wk 3-8)

    If continuation:

    150 mg/m2 iv, every 2nd wk

  • Drug: Cyclosporin

    WK 1-8:

    - Aim at around 200 microgram/L (trough value). Start: 6 mg/kg daily (divided in 2 daily doses) wk 1, if kidney function is normal.

    If continuation:

    - Aim for around 200 microgram/L. Monitor GFR.

  • Procedure: Intrathecal therapy

    If at 2 wks there are progressive neurological symptoms or if an abnormal CSF (cell count and protein) has not improved, then give 4 wkly intrathecal inj. Be aware that some pat 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
    The SCT procedure is up to the treating physician. However, a suggested regimen is provided.
Experimental: Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & Steroids

As compared to the HLH-94 treatment, the main changes are that

  1. Cyclosporin A is administered from day 1 and
  2. Intrathecal steroids are added to the intrathecal methotrexate.

Drugs, dosage, frequency and duration are described in the paragraph "Interventions" below.

  • Drug: Dexamethasone
  • Drug: Etoposide
  • Drug: Cyclosporin
  • Procedure: Intrathecal therapy
  • Procedure: Stem cell transplant
Henter JI, Horne A, Aricó 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
December 2017
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.
Sexes Eligible for Study: All
up to 18 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
Not Provided
Plan to Share IPD: Undecided
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
March 2017

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