Combination Chemotherapy in Treating Young Patients With Langerhans Cell Histiocytosis

January 9, 2014 updated by: Histiocyte Society

Treatment Protocol of the Third International Study For Langerhans Cell Histiocytosis

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of Langerhans cell histiocytosis, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may be an effective treatment for Langerhans cell histiocytosis.

PURPOSE: This randomized clinical trial is studying combination chemotherapy to see how well it works in treating young patients with Langerhans cell histiocytosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare the efficacy, in terms of response to initial therapy, of prednisolone, vinblastine, and mercaptopurine with vs without methotrexate and leucovorin calcium in young patients with Langerhans cell histiocytosis.
  • Compare the progression-free survival of patients with low-risk Langerhans cell histiocytosis who responded to initial therapy who are then treated with 6-month vs 12-month continuation therapy comprising prednisolone and vinblastine.

Secondary

  • Compare the acute and long-term toxicity and the incidence of permanent effects.
  • Compare the overall and progression-free survival, response rate, and time until response.

OUTLINE: This is a randomized, multicenter study with one pilot nonrandomized stratum. Patients are stratified according to number of systems involved (multiple vs single) and organs involved (at risk vs low risk).

  • Stratum 1 (at risk patients): Patients are further stratified according to participating center. Patients are randomized to 1 of 2 treatment arms (arms I and II).

    • Arm I:

      • Initial therapy: Patients receive oral prednisolone 3 times daily on days 1-28 followed by a taper on days 29-42 and vinblastine IV on days 1, 8, 15, 22, 29, and 36. Patients achieving nonactive disease (NAD) after course 1 proceed to continuation therapy. Patients achieving intermediate response or disease regression receive a second course* of initial therapy. Patients achieving NAD or disease regression after course 2 proceed to continuation therapy.
      • Continuation therapy: Patients receive oral mercaptopurine daily for 3 weeks, pulsed oral prednisolone 3 times daily on days 1-5, and vinblastine IV on day 1. Treatment repeats every 3 weeks until day 365 from the beginning of therapy in the absence of disease progression or unacceptable toxicity.

    • Arm II:

      • Initial therapy: Patients receive prednisone and vinblastine as in arm I initial therapy. Patients also receive methotrexate IV over 24 hours on days 1, 15, and 29 and oral leucovorin calcium twice daily on days 2,16, and 30. Patients achieving NAD after course 1 proceed to continuation therapy. Patients achieving intermediate response or disease regression receive a second course* of initial therapy. Patients achieving NAD or disease regression after course 2 proceed to continuation therapy.
      • Continuation therapy: Patients receive oral mercaptopurine daily for 3 weeks, pulsed oral prednisolone 3 times daily on days 1-5, vinblastine IV on day 1, and oral methotrexate on day 1. Treatment repeats every 3 weeks until day 365 from the beginning of therapy in the absence of disease progression or unacceptable toxicity.

  • Stratum 2 (low-risk patients): Patients are stratified according to age at diagnosis (≤ 2 vs > 2) and participating center. Patients are randomized to 1 of 2 treatment arms (arms III and IV) after the first course of initial therapy.

    • Arm III:

      • Initial therapy: Patients receive prednisolone and vinblastine as in course 1 of stratum 1 arm I initial therapy. Patients achieving NAD or disease regression after course 1 proceed to continuation therapy. Patients achieving intermediate or worse response receive a second course* of initial therapy. Patients achieving NAD, disease regression, or intermediate response after course 2 proceed to continuation therapy.
      • Continuation therapy: Patients receive prednisolone and vinblastine as in stratum 1 arm I continuation therapy. Treatment continues until day 182 from the beginning of initial therapy in the absence of disease progression or unacceptable toxicity.

    • Arm IV:

      • Initial therapy: Patients receive 1-2 courses of prednisolone and vinblastine as in stratum 2 arm III.
      • Continuation therapy: Patients receive pulsed prednisolone and vinblastine as in stratum 1 arm I continuation therapy. Treatment continues until day 365 from the beginning of initial therapy in the absence of disease progression or unacceptable toxicity.

  • Stratum 3 (pilot study) (patients with multifocal bone disease and/or special sites):

    • Initial therapy: Patients receive prednisolone and vinblastine as in stratum 1 arm I initial therapy. Patients achieving NAD or disease regression after course 1 proceed to continuation therapy. Patients with disease progression receive a second course* of initial therapy. Patients achieving NAD or disease regression after course 2 proceed to continuation therapy.
    • Continuation therapy: Patients receive pulsed prednisolone and vinblastine as in stratum 1 arm I continuation therapy. Treatment continues until day 182 from the beginning of initial therapy in the absence of disease progression or unacceptable disease.

NOTE: *Patients receive oral prednisolone 3 times daily on days 43-45, 50-52, 57-59, 64-66, 71-73, and 78-80 only during the second course of initial therapy.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 376 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

376

Phase

  • Not Applicable

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

  • Argentina
      • Buenos Aires, Argentina, 1245
        • Hospital de Pediatría Garrahan
  • Austria
      • Vienna, Austria, A-1090
        • St. Anna Children's Hospital
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
  • France
      • Nantes, France, 44093
        • CHR Hotel Dieu
  • Germany
      • Hamburg, Germany, D-20246
        • University Medical Center Hamburg - Eppendorf
  • Ireland
      • Dublin, Ireland, 12
        • Our Lady's Hospital for Sick Children Crumlin
  • Italy
      • Pavia, Italy, 27100
        • Fondazione I.R.C.C.S. Policlinico San Matteo
  • Sweden
      • Stockholm, Sweden, S-171 76
        • Karolinska University Hospital - Solna
  • United Kingdom
    • England
      • Birmingham, England, United Kingdom, B4 6NH
        • Birmingham Children's Hospital
      • Bristol, England, United Kingdom, BS2 8AE
        • Institute of Child Health at University of Bristol
      • Cambridge, England, United Kingdom, CB2 2QQ
        • Addenbrooke's Hospital
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
      • Leicester, England, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • Leicester, England, United Kingdom, LE1 6TH
        • Children's Cancer and Leukaemia Group
      • Liverpool, England, United Kingdom, L12 2AP
        • Royal Liverpool Children's Hospital, Alder Hey
      • London, England, United Kingdom, E1 1BB
        • Royal London Hospital
      • London, England, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for Children
      • Manchester, England, United Kingdom, M27 4HA
        • Royal Manchester Children's Hospital
      • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
        • Sir James Spence Institute of Child Health at Royal Victoria Infirmary
      • Nottingham, England, United Kingdom, NG7 2UH
        • Queen's Medical Centre
      • Oxford, England, United Kingdom, 0X3 9DU
        • Oxford Radcliffe Hospital
      • Sheffield, England, United Kingdom, S10 2TH
        • Children's Hospital - Sheffield
      • Southampton, England, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Sutton, England, United Kingdom, SM2 5PT
        • Royal Marsden - Surrey
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT12 6BE
        • Royal Belfast Hospital for Sick Children
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZG
        • Royal Aberdeen Children's Hospital
      • Edinburgh, Scotland, United Kingdom, EH9 1LF
        • Royal Hospital for Sick Children
      • Glasgow, Scotland, United Kingdom, G3 8SJ
        • Royal Hospital for Sick Children
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XW
        • Childrens Hospital for Wales
  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232-9700
        • Vanderbilt Children's Hospital
    • Texas
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center and Hematology Service at Texas Children's 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 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histopathologically confirmed diagnosis of Langerhans cell histiocytosis according to the criteria defined by the Histiocyte Society

    • Demonstration of CD1a antigenic determinants on the surface of lesional cells (by immunocytology or immunohistology) or Birbeck granules in lesional cells by electron microscopy

  • Considered at risk or low risk according to the following criteria:

    • Multi-system at risk disease, defined as involvement of one or more risk organs (i.e., hematopoietic system, liver, spleen, or lungs)

      • No single-system lung involvement

    • Multi-system low-risk disease

      • Multiple organs involved but without involvement of risk organs

    • Single-system disease

      • Multifocal bone disease (i.e., lesions in 2 or more different bones)

      • Localized special site involvement, such as CNS-risk lesions with intracranial soft tissue extension or vertebral lesions with intraspinal soft tissue extension

        • Vault lesions are not regarded as CNS-risk lesions

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior treatment for Langerhans cell histiocytosis

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: RANDOMIZED

Collaborators and Investigators

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

Sponsor

Histiocyte Society

Investigators

  • Study Chair: Kenneth L. McClain, MD, PhD, Texas Children's Cancer Center

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

April 1, 2001

Study Completion (ACTUAL)

June 1, 2013

Study Registration Dates

First Submitted

January 12, 2006

First Submitted That Met QC Criteria

January 12, 2006

First Posted (ESTIMATE)

January 13, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

January 10, 2014

Last Update Submitted That Met QC Criteria

January 9, 2014

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000454768
  • HISTSOC-LCH-III
  • CCLG-LCH-III
  • EU-20587
  • CCLG-LCH-2002-07
  • UMN-2006NT004

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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