Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

NCT ID: NCT00426101

Last Updated: 2018-07-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

368 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2017-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hemophagocytic Lymphohistiocytosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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.

Intrathecal therapy

Intervention Type PROCEDURE

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

Intervention Type PROCEDURE

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

Interventions

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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

Intervention Type 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

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

Stem cell transplant

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

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients who fulfil the diagnostic criteria of HLH.

Exclusion Criteria

* Prior cytotoxic or cyclosporin treatment for HLH.
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Meyer Children's Hospital IRCCS

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role collaborator

Ehime University Graduate School of Medicine

OTHER

Sponsor Role collaborator

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role collaborator

St. Anna Kinderkrebsforschung

OTHER

Sponsor Role collaborator

Hospital de Cruces

OTHER

Sponsor Role collaborator

Hospital JP Garrahan

OTHER_GOV

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jan-Inge Henter

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jan-Inge Henter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Childhood Cancer Research Unit, Karolinska Hospital

Stockholm, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type BACKGROUND
PMID: 16937360 (View on PubMed)

Bergsten 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.

Reference Type RESULT
PMID: 28935695 (View on PubMed)

Bergsten 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.

Reference Type DERIVED
PMID: 32780845 (View on PubMed)

Other Identifiers

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HLH-2004

Identifier Type: -

Identifier Source: org_study_id

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