Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

Hemophagocytic Lymphohistiocytosis Clinical Trial

Official title:

HLH-2004 Treatment Protocol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00426101
• Other study ID #: HLH-2004
• Status: Completed
• Phase: Phase 3
• Start date: January 2004
• Est. completion date: December 2017

Study information

• Verified date: July 2018
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 368
• Est. completion date: December 2017
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Patients who fulfil the diagnostic criteria of HLH.

Exclusion Criteria:

• Prior cytotoxic or cyclosporin treatment for HLH.

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Intervention

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
• 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
• 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.
• Stem cell transplant
The SCT procedure is up to the treating physician. However, a suggested regimen is provided.

Locations

Country	Name	City	State
Sweden	Childhood Cancer Research Unit, Karolinska Hospital	Stockholm

Sponsors (11)

Lead Sponsor	Collaborator
Karolinska University Hospital	Azienda Ospedaliero, Universitaria Meyer, Children's Hospital Medical Center, Cincinnati, Ehime University Graduate School of Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, Hospital de Cruces, Hospital JP Garrahan, Leiden University Medical Center, St. Anna Kinderkrebsforschung, Texas Children's Hospital, Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

Bergsten E, Horne A, Aricó M, Astigarraga I, Egeler RM, Filipovich AH, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Montgomery S, Nanduri V, Rosso D, Henter JI. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-ter — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		1-year after diagnosis
Secondary	Late effects		5-years after diagnosis