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Clinical Trials (PDQ®)

  • First Published: 1/6/2006
  • Last Modified: 4/10/2013

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Randomized and Pilot Study of Risk-Adapted Therapy Comprising Prednisolone, Vinblastine, and Mercaptopurine With Versus Without Methotrexate and Leucovorin Calcium or Prednisolone and Vinblastine in Young Patients With Langerhans Cell Histiocytosis. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Young Patients With Langerhans Cell Histiocytosis. Note: The information about this trial has not been updated by the sponsor/principal investigator/lead organization. Cancer.gov cannot verify the accuracy of the information.

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
No phase specifiedTreatmentClosedUnder 18OtherHISTSOC-LCH-III
CCLG-LCH-III, EU-20587, CCLG-LCH-2002-07, NCT00276757, UMN-2006NT004

Objectives

Primary

  1. 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.
  2. 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

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

Entry Criteria

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

Prior/Concurrent Therapy:

  • No prior treatment for Langerhans cell histiocytosis

Patient Characteristics:

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

Expected Enrollment

376

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

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.

Trial Contact Information

Trial Lead Organizations

Histiocyte Society

Kenneth McClain, MD, PhD, Protocol chair
Ph: 832-822-4208
Email: klmcclai@txch.org

Registry Information
Official Title Treatment Protocol of the Third International Study For Langerhans Cell Histiocytosis
Trial Start Date 2001-04-01
Registered in ClinicalTrials.gov NCT00276757
Date Submitted to PDQ 2005-09-15
Information Last Verified 2007-05-27

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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