Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

• Sponsor: Karolinska University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00426101
• Collaborator: Azienda Ospedaliero, Universitaria Meyer (Other), Leiden University Medical Center (Other), Children's Hospital Medical Center, Cincinnati (Other), Ehime University Graduate School of Medicine (Other), Universitätsklinikum Hamburg-Eppendorf (Other), Baylor College of Medicine (Other), Great Ormond Street Hospital for Children NHS Foundation Trust (Other), St. Anna Kinderkrebsforschung (Other), Hospital de Cruces (Other), Hospital JP Garrahan (Other)
• Enrollment: 368
• Location: 1
• Arm: 1
• Duration (Months): 167
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hemophagocytic Lymphohistiocytosis	Drug: Dexamethasone; Drug: Etoposide; Drug: Cyclosporin; Procedure: Intrathecal therapy; Procedure: Stem cell transplant	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 368 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: HLH-2004 Treatment Protocol
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & Steroids As compared to the HLH-94 treatment, the main changes are that Cyclosporin A is administered from day 1 and Intrathecal steroids are added to the intrathecal methotrexate. Drugs, dosage, frequency and duration are described in the paragraph "Interventions" below.

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.

Outcome Measures

Primary Outcome Measures

1. Survival [1-year after diagnosis]

Secondary Outcome Measures

1. Late effects [5-years after diagnosis]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who fulfil the diagnostic criteria of HLH.

Exclusion Criteria:

• Prior cytotoxic or cyclosporin treatment for HLH.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childhood Cancer Research Unit, Karolinska Hospital	Stockholm		Sweden	S-171 76

Sponsors and Collaborators

• 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
• Baylor College of Medicine
• Great Ormond Street Hospital for Children NHS Foundation Trust
• St. Anna Kinderkrebsforschung
• Hospital de Cruces
• Hospital JP Garrahan

Investigators

• Principal Investigator: Jan-Inge Henter, MD, PhD, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Jan-Inge Henter, Professor, Karolinska University Hospital
• ClinicalTrials.gov Identifier: NCT00426101
• Other Study ID Numbers: HLH-2004
• First Posted: Jan 24, 2007
• Last Update Posted: Jul 5, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Jan-Inge Henter, Professor, Karolinska University Hospital: Hemophagocytic lymphohistiocytosis
• Additional relevant MeSH terms: Lymphohistiocytosis, Hemophagocytic; Cyclosporine; Dexamethasone; Etoposide; Cyclosporins

Study Results

No Results Posted as of Jul 5, 2018