Combination Chemotherapy in Treating Young Patients With Langerhans Cell Histiocytosis

Childhood Langerhans Cell Histiocytosis Clinical Trial

Official title:

Treatment Protocol of the Third International Study For Langerhans Cell Histiocytosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00276757
• Other study ID #: CDR0000454768
• Secondary ID: HISTSOC-LCH-IIIC
• Status: Completed
• Phase: N/A
• First received: January 12, 2006
• Last updated: January 9, 2014
• Start date: April 2001
• Est. completion date: June 2013

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 376
• Est. completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Langerhans Cell Histiocytosis
• Histiocytosis
• Histiocytosis, Langerhans-Cell

Intervention

Drug:
• leucovorin calcium

• methotrexate

• prednisolone

• vinblastine sulfate

Locations

Country	Name	City	State
Argentina	Hospital de Pediatria Garrahan	Buenos Aires
Austria	St. Anna Children's Hospital	Vienna
Canada	Hospital for Sick Children	Toronto	Ontario
France	CHR Hotel Dieu	Nantes
Germany	University Medical Center Hamburg - Eppendorf	Hamburg
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
Italy	Fondazione I.R.C.C.S. Policlinico San Matteo	Pavia
Sweden	Karolinska University Hospital - Solna	Stockholm
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Institute of Child Health at University of Bristol	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Children's Cancer and Leukaemia Group	Leicester	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	Royal London Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Houston	Texas
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt Children's Hospital	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Histiocyte Society

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Canada,  France,  Germany,  Ireland,  Italy,  Sweden,  United Kingdom,