Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

July 2, 2018 updated by: Jan-Inge Henter, Karolinska University Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

368

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, S-171 76
        • Childhood Cancer Research Unit, Karolinska Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 14 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients who fulfil the diagnostic criteria of HLH.

Exclusion Criteria:

  • Prior cytotoxic or cyclosporin treatment for HLH.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival
Time Frame: 1-year after diagnosis
1-year after diagnosis

Secondary Outcome Measures

Outcome Measure
Time Frame
Late effects
Time Frame: 5-years after diagnosis
5-years after diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska University Hospital

Collaborators

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

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

January 23, 2007

First Submitted That Met QC Criteria

January 23, 2007

First Posted (Estimate)

January 24, 2007

Study Record Updates

Last Update Posted (Actual)

July 5, 2018

Last Update Submitted That Met QC Criteria

July 2, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLH-2004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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