This trial is active, not recruiting.

Condition hemophagocytic lymphohistiocytosis
Treatments dexamethasone, etoposide, cyclosporin, intrathecal therapy, stem cell transplant
Phase phase 3
Sponsor Karolinska University Hospital
Collaborator Azienda Ospedaliero, Universitaria Meyer
Start date January 2004
End date December 2011
Trial size 300 participants
Trial identifier NCT00426101, HLH-2004


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
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.
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.
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.
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: 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. 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.

Primary Outcomes

time frame: 1-year after diagnosis

Secondary Outcomes

Late effects
time frame: 5-years after diagnosis

Eligibility Criteria

Male or female participants up to 18 years old.

Inclusion Criteria: - Patients who fulfil the diagnostic criteria of HLH. Exclusion Criteria: - Prior cytotoxic or cyclosporin treatment for HLH.

Additional Information

Official title HLH-2004 Treatment Protocol
Principal investigator Jan-Inge Henter, MD, PhD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Karolinska University Hospital.