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Hemophagocytic LymphohistiocytosisPhase 3NCT00426101

Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

A Phase 3 study testing Dexamethasone, Etoposide and Cyclosporin in people with Hemophagocytic Lymphohistiocytosis, run by Karolinska University Hospital at 1 site in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Hemophagocytic Lymphohistiocytosis
What is being tested?
Dexamethasone, Etoposide and Cyclosporin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
368 participants
Where
1 siteSweden
Study dates
Jan 2004to Dec 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients who fulfil the diagnostic criteria of HLH.

Who cannot join

  • Prior cytotoxic or cyclosporin treatment for HLH.

Trial locations and contacts

1 site in 1 country.

Sweden1 site

  • Childhood Cancer Research Unit, Karolinska Hospital

    Stockholm, S-171 76

Other trials in Sweden

About this study

Official title: HLH-2004 Treatment Protocol

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.

Read the 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.

Being tested
Dexamethasone, Etoposide, Cyclosporin, Intrathecal therapy, Stem cell transplant
Keywords
Hemophagocytic lymphohistiocytosis
Medical subject headings
Lymphohistiocytosis, Hemophagocytic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexamethasoneDrug

    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

  • EtoposideDrug

    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

  • CyclosporinDrug

    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 therapyProcedure or surgery

    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 transplantProcedure or surgery

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

Study groups in NCT00426101
Study groupRoleWhat they receive
Etoposide, Dexamethasone, Cyclosporin A plus IT MTX & SteroidsExperimentalAs 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.
Receives: Drug: Dexamethasone; Drug: Etoposide; Drug: Cyclosporin; Procedure: Intrathecal therapy; Procedure: Stem cell transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Survival

    Measured: 1-year after diagnosis

Secondary outcomes (1)

  1. Late effects

    Measured: 5-years after diagnosis

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jan 2007 (estimated)
  2. Study startJan 2004
  3. Primary completionDec 2011
  4. Study completionDec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
368 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00426101
Sponsor's protocol ID
HLH-2004
Status last verified
Jul 2018
First submitted
23 Jan 2007
Last updated
5 Jul 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 16937360

  • 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.

    PubMed 28935695

  • Bergsten E, Arico M, Astigarraga I, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Nanduri V, Rosso DA, Sieni E, Horne A, Henter JI. Central Nervous System Involvement in Children with Hemophagocytic Lymphohistiocytosis: an HLH-2004 Study Report. Blood Adv. 2026 Aug 21:bloodadvances.2026020485. doi: 10.1182/bloodadvances.2026020485. Online ahead of print.

    PubMed 42628036

  • 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.

    PubMed 32780845

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dexamethasone, Etoposide and Cyclosporin in people with Hemophagocytic Lymphohistiocytosis, run by Karolinska University Hospital at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival (time frame: 1-year after diagnosis). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00426101, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.

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