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: November 22, 2012
Last verified: November 2012
  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: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HLH-2004 Treatment Protocol

Resource links provided by NLM:


Further study details as provided by Karolinska University Hospital:

Primary Outcome Measures:
  • Survival [ Time Frame: 1-year after diagnosis ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Late effects [ Time Frame: At last follow-up report ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: January 2004
Estimated Study Completion Date: December 2016
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Dexamethasone
    • Dexamethasone 10 mg/m2 daily, for the first 2 weeks (week 1-2).
    • Dexamethasone 5 mg/m2 daily, for another 2 weeks (week 3-4).
    • Dexamethasone 2.5 mg/m2 daily, for another 2 weeks (week 5-6)
    • Dexamethasone 1.25 mg/m2 daily, for another week (week 7). Steroids are tapered and discontinued during week 8.

    If continuation therapy is provided, then:

    - Dexamethasone pulses every second week, 10 mg/m2 for 3 days.

    Drug: Etoposide
    • 150 mg/m2 iv twice weekly (week 1-2).
    • 150 mg/m2 iv once weekly (week 3-8).

    If continuation therapy is provided, then:

    - 150 mg/m2 iv, every second week.

    Drug: Cyclosporin

    WEEK 1-8:

    - The blood levels determine the dosages, aim at levels around 200 microgram/L (trough value) (monoclonal antibody assay of whole blood). Start with 6 mg/kg daily (divided in 2 daily doses) already week 1, if kidney function is normal.

    If continuation therapy is provided, then:

    - Aim for blood levels around 200 microgram/L, as above. Monitor GFR.

    Procedure: Intrathecal therapy

    The CSF is evaluated at diagnosis and after 2 weeks. If after 2 weeks there is clinical evidence of progressive neurological symptoms or if an abnormal CSF (cell count and protein) has not improved, additional CNS-therapy is initiated with 4 weekly intrathecal injections. Be aware that some patients 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

    Suggested regimen:

    Preparative Regimen

    • Day -8,-7,-6,-5 Busulfan 2mg/kg po, or eq iv (as 1.6mg/kg), twice daily.
    • Day -4 Etoposide 30 mg/kg iv (6 hr inf) (maximum 1800 mg)
    • Day -3, -2 Cyclophosphamide 60 mg/kg iv (1 hr inf)
    • Day 0 Marrow infusion (preferably ³3 x 108 nucleated cells/kg, non T-cell-depleted).

    GVHD Prophylaxis:

    1. CSA continuous infusion starting day -1 pre-transplant with 3 mg/kg until oral nutrition re-established, thereafter 12.5 mg/kg orally daily. Monitoring of CSA through concentration levels. The immunosuppression is discontinued after 6-12 months, if possible.
    2. Short course methotrexate:

      • Day +1 15 mg/m2 iv
      • Day +3 10 mg/m2 iv
      • Day +6 10 mg/m2 iv Methotrexate may be substituted by mycophenolate mofetil (MMF).

    Additional Treatment for URD

    • ATG (12 hr inf iv) on days -3, -2 and -1 (according to manufacturers rec).
    • Metronidazole 22 mg/kg daily (po or iv) from day -8 until discharge.
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
Genders Eligible for Study:   Both
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: November 22, 2012
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by Karolinska University Hospital:
Hemophagocytic lymphohistiocytosis

Additional relevant MeSH terms:
Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Cyclosporins
Cyclosporine
BB 1101
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Etoposide phosphate
Etoposide
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on July 26, 2014