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Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Azienda Ospedaliero, Universitaria Meyer
Leiden University Medical Center
Children's Hospital Medical Center, Cincinnati
Ehime University Graduate School of Medicine
Universitätsklinikum Hamburg-Eppendorf
Texas Children's Hospital
Great Ormond Street Hospital for Children NHS Foundation Trust
St. Anna Kinderkrebsforschung
Hospital de Cruces
Hospital JP Garrahan
Information provided by (Responsible Party):
Jan-Inge Henter, Karolinska University Hospital
ClinicalTrials.gov Identifier:
NCT00426101
First received: January 23, 2007
Last updated: March 12, 2017
Last verified: March 2017
  Purpose
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 Intervention Phase
Hemophagocytic Lymphohistiocytosis Drug: Dexamethasone Drug: Etoposide Drug: Cyclosporin Procedure: Intrathecal therapy Procedure: Stem cell transplant Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: HLH-2004 Treatment Protocol

Resource links provided by NLM:


Further study details as provided by Jan-Inge Henter, Karolinska University Hospital:

Primary Outcome Measures:
  • Survival [ Time Frame: 1-year after diagnosis ]

Secondary Outcome Measures:
  • Late effects [ Time Frame: 5-years after diagnosis ]

Estimated Enrollment: 300
Study Start Date: January 2004
Estimated Study Completion Date: December 2017
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who fulfil the diagnostic criteria of HLH.

Exclusion Criteria:

  • Prior cytotoxic or cyclosporin treatment for HLH.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00426101

Locations
Sweden
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
Texas Children's Hospital
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
  More Information

Publications:
Responsible Party: Jan-Inge Henter, Professor, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT00426101     History of Changes
Other Study ID Numbers: HLH-2004
Study First Received: January 23, 2007
Last Updated: March 12, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Jan-Inge Henter, Karolinska University Hospital:
Hemophagocytic lymphohistiocytosis

Additional relevant MeSH terms:
Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Dexamethasone acetate
Dexamethasone
Etoposide phosphate
Etoposide
BB 1101
Cyclosporins
Cyclosporine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 22, 2017