Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004
HLH-2004 Treatment Protocol
1 other identifier
interventional
368
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2004
Longer than P75 for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2004
CompletedFirst Submitted
Initial submission to the registry
January 23, 2007
CompletedFirst Posted
Study publicly available on registry
January 24, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2017
CompletedJuly 5, 2018
July 1, 2018
7.9 years
January 23, 2007
July 2, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Survival
1-year after diagnosis
Secondary Outcomes (1)
Late effects
5-years after diagnosis
Study Arms (1)
Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & Steroids
EXPERIMENTALAs 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.
Interventions
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
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
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.
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.
The SCT procedure is up to the treating physician. However, a suggested regimen is provided.
Eligibility Criteria
You may qualify if:
- Patients who fulfil the diagnostic criteria of HLH.
You may not qualify if:
- Prior cytotoxic or cyclosporin treatment for HLH.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Karolinska University Hospitallead
- Meyer Children's Hospital IRCCScollaborator
- Leiden University Medical Centercollaborator
- Children's Hospital Medical Center, Cincinnaticollaborator
- Ehime University Graduate School of Medicinecollaborator
- Universitätsklinikum Hamburg-Eppendorfcollaborator
- Baylor College of Medicinecollaborator
- Great Ormond Street Hospital for Children NHS Foundation Trustcollaborator
- St. Anna Kinderkrebsforschungcollaborator
- Hospital de Crucescollaborator
- Hospital JP Garrahancollaborator
Study Sites (1)
Childhood Cancer Research Unit, Karolinska Hospital
Stockholm, S-171 76, Sweden
Related Publications (3)
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. doi: 10.1002/pbc.21039.
PMID: 16937360BACKGROUNDBergsten E, Horne A, Arico 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-term results of the cooperative HLH-2004 study. Blood. 2017 Dec 21;130(25):2728-2738. doi: 10.1182/blood-2017-06-788349. Epub 2017 Sep 21.
PMID: 28935695RESULTBergsten E, Horne A, Hed Myrberg I, Arico M, Astigarraga I, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Nanduri V, Rosso DA, Sieni E, Winiarski J, Henter JI. Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study. Blood Adv. 2020 Aug 11;4(15):3754-3766. doi: 10.1182/bloodadvances.2020002101.
PMID: 32780845DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jan-Inge Henter, MD, PhD
Karolinska Institutet
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
January 23, 2007
First Posted
January 24, 2007
Study Start
January 1, 2004
Primary Completion
December 1, 2011
Study Completion
December 1, 2017
Last Updated
July 5, 2018
Record last verified: 2018-07