Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

LCH-IV, International Collaborative Treatment Protocol voor kinderen en adolescenten met Langerhans-celhistiocytose

9 november 2026 bijgewerkt door: North American Consortium for Histiocytosis

The LCH-IV is an international, multicenter, prospective clinical study for pediatric Langerhans Cell Histiocytosis LCH (age < 18 years).

Studie Overzicht

Toestand

Actief, niet wervend

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

The international efforts of the past 20 years have shown that combination therapy with vinblastine and prednisone is an effective therapy for Multi-system (MS)-LCH. The previous prospective trial LCH-III confirmed this regimen as a standard regimen for MS-LCH in patients with and without risk organ involvement. It also showed that prolonged treatment in the latter group (treatment duration of 12 vs. 6 months) is superior in preventing disease reactivations. The results of this trial are encouraging and serve as a basis for the LCH-IV study design.Due to the complexity of the disease presentations and outcomes, the LCH-IV study seeks to tailor treatment based on features at presentation and on response to treatment, leading to seven strata:

  • Stratum I: First-line treatment for MS-LCH patients (Group 1) and patients with Single system (SS)-LCH with multifocal bone or "Central Nervous System (CNS)-risk" lesions (Group 2)
  • Stratum II: Second-line treatment for non-risk patients (patients without risk organ involvement who fail first-line therapy or have a reactivation after completion of first-line therapy)
  • Stratum III: Salvage treatment for risk LCH (patients with dysfunction of risk organs who fail first-line therapy)
  • Stratum IV: Stem cell transplantation for risk LCH (patients with dysfunction of risk organs who fail first-line therapy)
  • Stratum V: Monitoring and treatment of isolated tumorous and neurodegenerative CNS-LCH
  • Stratum VI: Natural history and management of "other" SS-LCH (patients who do not need systemic therapy at the time of diagnosis)
  • Stratum VII: Long-term Follow up (all patients irrespective of previous therapy will be followed for reactivation or permanent consequences once complete disease resolution has been achieved and the respective protocol treatment completed)

Studietype

Ingrijpend

Inschrijving (Werkelijk)

1400

Fase

  • Fase 2
  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Alabama
      • Birmingham, Alabama, Verenigde Staten, 35233
        • Children's of Alabama
    • Arizona
      • Phoenix, Arizona, Verenigde Staten, 85006
        • Phoenix Children's Hospital
    • Arkansas
      • Little Rock, Arkansas, Verenigde Staten, 72202
        • Arkansas Children's Hospital
    • California
      • Los Angeles, California, Verenigde Staten, 90027
        • Children's Hospital of Los Angeles
      • Madera, California, Verenigde Staten, 93636
        • Valley Children's Healthcare
      • Oakland, California, Verenigde Staten, 94609
        • UCSF Benioff Children's Hospital of Oakland
      • Orange, California, Verenigde Staten, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, Verenigde Staten, 94158-0106
        • UCSF Helen Diller Family Cancer Center
    • Connecticut
      • Hartford, Connecticut, Verenigde Staten, 06106
        • Connecticut Children's Medical Center
    • District of Columbia
      • Washington D.C., District of Columbia, Verenigde Staten, 20010
        • Children's National Medical Center
    • Florida
      • St. Petersburg, Florida, Verenigde Staten, 33701
        • Johns Hopkins All Children's Hospital
    • Georgia
      • Atlanta, Georgia, Verenigde Staten, 30342
        • Children's Healthcare of Atlanta, Emory
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611-2991
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis, Indiana, Verenigde Staten, 46202
        • Riley Hospital for Children - Indiana University
    • Kansas
      • Kansas City, Kansas, Verenigde Staten, 64108
        • Children's Mercy Hospitals
    • Kentucky
      • Lexington, Kentucky, Verenigde Staten, 40536
        • University of Kentucky A.B.Chandler Medical Center
      • Louisville, Kentucky, Verenigde Staten, 40202
        • University of Louisville, Norton Children's Hospital
    • Maryland
      • Baltimore, Maryland, Verenigde Staten, 21287
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, Verenigde Staten, 02115
        • Dana Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, Verenigde Staten, 55404
        • Children's Minnesota
    • New Jersey
      • Hackensack, New Jersey, Verenigde Staten, 07601
        • Hackensack University Medical Center
    • New York
      • New Hyde Park, New York, Verenigde Staten, 11040
        • Cohen Children's Medical Center
      • New York, New York, Verenigde Staten, 10029
        • Mount Sinai Hospital
      • New York, New York, Verenigde Staten, 10032
        • Columbia University / Herbert Irving Cancer Center
      • New York, New York, Verenigde Staten, 10170
        • Memorial Sloan Kettering Cancer Center
      • Syracuse, New York, Verenigde Staten, 13210
        • SUNY Upstate Medical University
      • The Bronx, New York, Verenigde Staten, 10467
        • Children's Hospital at Montefiore
    • North Carolina
      • Charlotte, North Carolina, Verenigde Staten, 28203
        • Carolinas Medical Center, Levine Children's Hospital
    • Ohio
      • Akron, Ohio, Verenigde Staten, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, Verenigde Staten, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, Verenigde Staten, 44106
        • Rainbow Babies & Children's Hospital, University Hospitals
      • Toledo, Ohio, Verenigde Staten, 43606
        • Russell J Ebeid Children's Hospital (Promedica)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Verenigde Staten, 15224
        • UPMC Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, Verenigde Staten, 29425
        • Medical University of South Carolina (MUSC)
      • Greenville, South Carolina, Verenigde Staten, 29605
        • Greenville Health System BI-LO Charities Children's Cancer Center
    • Tennessee
      • Memphis, Tennessee, Verenigde Staten, 38105
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, Verenigde Staten, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, Verenigde Staten, 75235
        • Children's Medical Center Dallas, UT Southwestern
    • Washington
      • Spokane, Washington, Verenigde Staten, 99204
        • Providence Sacred Heart Children's Hospital
      • Tacoma, Washington, Verenigde Staten, 98431
        • Madigan Army Medical Center
    • Wisconsin
      • Madison, Wisconsin, Verenigde Staten, 53792
        • American Family Children's Hospital University of Wisconsin

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

Niet ouder dan 18 jaar (Kind, Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Stratum I

    • Patients must be less than 18 years of age at the time of diagnosis.
    • Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1
    • Signed informed consent form

  • Stratum II

    • Patients of Stratum I who have:
    • Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
    • AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2)
    • Disease progression (AD worse) in non-risk organs at any time during continuation treatment
    • Active disease at the end of Stratum I treatment
    • Disease reactivation in non-risk organs at any time after completion of Stratum I treatment

  • Stratum III

    • Patients from Stratum I who fulfill the following criteria:

    • AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2).

    • Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as

      • Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
      • PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR
      • Liver dysfunction (or digestive involvement with protein loss)
      • Total protein <55 g/L or substitution dependency
      • Albumin <25 g/L or substitution dependency (at least one of the two criteria to be fulfilled)

  • Stratum IV

    • Patients from Stratum I or Stratum III who fulfill the following criteria:
    • AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I OR
    • AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
    • Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as defined in Table XI (see Section 10.3.1).
    • Informed consent: All patients or their legal guardians (if the patient is <18 years of age) must sign an Ethics or institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study. When appropriate, younger patients will be included in all discussions in order to obtain assent.
    • Adequate organ function: Patients should have adequate hepatic, renal, cardiac and pulmonary function to undergo reduced intensity HCT based upon local institutional guidelines, or at a minimum meet requirements noted in eligibility checklist Appendix A-VIII_1. However, significant hepatic and pulmonary dysfunction, if secondary to underlying LCH disease activity, will not exclude patients from protocol enrollment and should be discussed with the National PI Coordinator and the Coordinating Principal Investigator.

  • Stratum V

    • All patients with verified diagnosis of LCH and MRI findings consistent with ND-CNSLCH irrespective of previous treatments (also those not registered to other Strata ofLCH-IV).
    • Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion in the hypothalamus-pituitary axis). In patients with already established diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion is needed for inclusion into the study

  • Stratum VI

    -- Patients with newly diagnosed SS-LCH and localization other than "multifocal bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.

  • Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as consent for longterm follow-up has not been withheld.

Exclusion Criteria:

  • Stratum I

    • Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy)
    • LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease
    • Prior systemic therapy

  • Stratum II

    • Patients with progressive disease in risk organs
    • Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations
    • No written consent of the patient or his/her parents or legal guardian

  • Stratum III

    • The presence of any of the following criteria will exclude the patient from the study:
    • Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement.
    • Inadequate renal function as defined by serum creatinine > 3x normal for age

  • Stratum IV

    • Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
    • Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
    • Uncontrolled active life-threatening infection.
    • Decreased renal function with a GFR of less than 50ml/1.73m2/min.
    • Pregnancy or active breast feeding
    • Failure to provide signed informed consent

  • Stratum VI

    • Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible for Stratum V),
    • Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible for Stratum I, Group 2)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Stratum I

Stratum I The combination of Prednisone and vinblastine is the standard first-line combination for patients needing systemic therapy (Stratum I). Patients with MS-LCH and involvement of risk organs, who do not respond to 6-12 weeks of standard therapy, will be immediately switched to alternative treatment approaches (Stratum III or Stratum IV).

Further therapy prolongation (12 vs. 24 months) and intensification (± mercaptopurine) will further reduce the reactivation rate and the permanent consequences.
Geneesmiddel: Prednisone

Stratum I

Geneesmiddel: Vinblastine

Stratum I

Andere namen:
  • Velban®
  • Vincaleukoblastinesulfaat
Geneesmiddel: mercaptopurine

Stratum I

Andere namen:
  • -Purinethol®
  • -6 MP
Experimenteel: Stratum II

A uniform "intensive" 24-week course consisting of prednisolone, vincristine and cytosine-arabinoside will be introduced in Stratum II for eligible patients. It will be followed by a continuation therapy to total treatment duration of 24 months. Participants who after SL-IT (week 24) have a response (NAD or AD better) are eligible for randomization between the continuation arms "INDOMETHACIN" and "6-MP/MTX" (mercaptopurine and Methotrexate).
Geneesmiddel: Cytosine arabinoside
Andere namen:
  • Cytarabine, Ara-C
Geneesmiddel: Prednisone

Stratum I

Geneesmiddel: Vinblastine

Stratum I

Andere namen:
  • Velban®
  • Vincaleukoblastinesulfaat
Geneesmiddel: mercaptopurine

Stratum I

Andere namen:
  • -Purinethol®
  • -6 MP
Geneesmiddel: INDOMETHACIN

Indomethacin fixed dose given daily orally in two divided doses with gastric protection for total treatment duration of 24 months.

Geneesmiddel: Methotrexate

fixed dose weekly orally for total treatment duration of 24 months.
Experimenteel: Stratum III

Salvage treatment for risk LCH To assess the efficacy of the combination 2-CdA/Ara-C (Cytosine Arabinoside and 2-chlorodeoxyadenosine) in MS-LCH (patients with risk organ involvement, who fail to respond to front-line (Stratum I) therapy.

The initial therapy consists of 2 courses of 2-CdA/Ara-C. Continuation of outlined treatment to be assessed at assigned intervals in each stratum.
Geneesmiddel: 2-chloordeoxyadenosine
Andere namen:
  • Leustatin®
  • 2-Cda
  • Cladribin®
Experimenteel: Stratum IV

To determine the overall and disease free survival at 1 and 3 years after reduced intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT). Salvage treatment option for MS-LCH patients with risk organ involvement, who fail to respond to front-line therapy (Stratum I) OR to the salvage 2- CdA/Ara-C regimen (Stratum III).
Procedure: hematopoëtische stamceltransplantatie (RIC-HSCT)
Experimenteel: Stratum V

Stratum V Monitoring and Treatment of isolated tumorous and neurodegenerative CNS-LCH

- Special regimens will be offered to patients with isolated tumorous CNS-LCH (repeated 2-CdA courses) and to patients with clinically manifested ND-CNS-LCH (+/- extracranial LCH manifestations). For the last group monotherapy with Ara-C courses or (Intravenous immunoglobulin)IVIG will be offered depending on physician's choice.
Geneesmiddel: Cytosine arabinoside
Andere namen:
  • Cytarabine, Ara-C
Geneesmiddel: 2-chloordeoxyadenosine
Andere namen:
  • Leustatin®
  • 2-Cda
  • Cladribin®
Biologisch: Intraveneus immunoglobuline
Andere namen:
  • IVIG
Experimenteel: Stratum VI

Natural history and management of "other" SS-LCH not eligible for stratum I group 2.

  • Treatment Options- Management (mostly "wait & see" and topical treatment) is left to the discretion of the treating physician. All treatments and disease responses must be reported in the database. In the case of uncertainties please contact your National Coordinator.
  • Patients being followed on Stratum VI who have progression of disease to MSLCH, multifocal bone disease or CNS-risk bone lesions should be enrolled on Stratum I therapy.
  • Patients being followed on Stratum VI who develop isolated tumorous or neurodegenerative CNS-LCH should be enrolled on Stratum V.
Geneesmiddel: Cytosine arabinoside
Andere namen:
  • Cytarabine, Ara-C
Geneesmiddel: 2-chloordeoxyadenosine
Andere namen:
  • Leustatin®
  • 2-Cda
  • Cladribin®
Biologisch: Intraveneus immunoglobuline
Andere namen:
  • IVIG
Geneesmiddel: Prednisone

Stratum I

Geneesmiddel: Vinblastine

Stratum I

Andere namen:
  • Velban®
  • Vincaleukoblastinesulfaat
Geneesmiddel: mercaptopurine

Stratum I

Andere namen:
  • -Purinethol®
  • -6 MP

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Patients with Reactivation Free Survival
Tijdsspanne: 12 Months

Stratum I, II, VI
12 Months
Response Rate of Second Cycle
Tijdsspanne: 9 weeks

Stratum III
9 weeks
Overall and disease free survival at 1 and 3 years after reduced intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT)
Tijdsspanne: 3 Years

Stratum IV
3 Years
The cumulative incidence of radiological and clinical neurodegeneration in patients with isolated tumorous CNS-LCH, DI, anterior pituitary dysfunction, and those with CNS-risk lesions
Tijdsspanne: 2 Years

Stratum V
2 Years
The time interval and cumulative incidence of progression of radiological neurodegeneration to clinically manifested ND-CNS-LCH
Tijdsspanne: 2 Years

Stratum V
2 Years
Cumulative incidence of specific Permanent Consequences e.g. diabetes insipidus (DI), growth hormone deficiency (GHD), neuropsychological impairment, etc.
Tijdsspanne: 2 Years

From all treatment stratum via long-term follow up in Stratum VII
2 Years

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Aantal deelnemers met ernstige en niet-ernstige bijwerkingen
Tijdsspanne: 2 jaar
2 jaar
Cumulatieve incidentie van reactiveringen in risicoorganen
Tijdsspanne: 2 jaar
2 jaar
Incidentie van hematopoëtisch herstel en donorchimerisme op d+100 en 1 jaar na RIC-HSCT
Tijdsspanne: 2 jaar
2 jaar
Identificeer mogelijke risicofactoren voor blijvende gevolgen (PC)
Tijdsspanne: 2 jaar
2 jaar
Overall Survival
Tijdsspanne: 2 Years

Stratum I
2 Years
Incidence of Permanent Consequences
Tijdsspanne: 2 Years

All Stratum
2 Years
Time to complete disease resolution
Tijdsspanne: 2 Years

Stratum III
2 Years
Response rate to the combination of prednisone, vincristine and cytarabine
Tijdsspanne: 2 years

Stratum II
2 years
The proportion of patients alive and free of disease without permanent consequences (e.g. diabetes insipidus, anterior pituitary dysfunction, radiological or clinical neurodegeneration)
Tijdsspanne: 2 Years

Stratum II
2 Years
Percentage of treatment-related toxicities
Tijdsspanne: 2 Years

Stratum II
2 Years
Reactivation rates after continuation treatment with Indomethacin vs. 6-MP/MTX.
Tijdsspanne: 2 years

Stratum II
2 years
The type of subsequent intensive and/or maintenance therapy utilized
Tijdsspanne: 2 Years

Stratum III
2 Years
Early and late mortality
Tijdsspanne: 2 Years

Stratum II
2 Years
Early and late toxicity
Tijdsspanne: 2 Years

Stratum III
2 Years
d+100 transplant related mortality
Tijdsspanne: 2 Years

Stratum IV
2 Years
Record all occurrence of skin, GI or liver abnormalities fulfilling criteria of Grades II-IV acute GVHD
Tijdsspanne: 2 Years

Stratum IV: Hematopoetic Stem Cell Transplantation for Risk LCH
2 Years
Percentage of Participants with incidence of chronic GVHD
Tijdsspanne: 2 Years

Stratum IV
2 Years
Response Rate to ND-CNS-targeted therapy at 12 and 24 months after start of therapy
Tijdsspanne: 2 years

Stratum V
2 years
Response of isolated tumorous CNS-LCH to 2-CDA
Tijdsspanne: 2 Years

Stratum V
2 Years
Frequency of ND-CNS-LCH in patients with isolated tumorous CNS-LCH
Tijdsspanne: 2 Years

Stratum V
2 Years
Methods of early identification of ND-CNS-LCH
Tijdsspanne: 2 Years

Stratum V - Exploration of the value of neurochemistry, neurophysiology, and neuropsychology methods in early identification of ND-CNS-LCH and in assessing its severity, and comparison to MRI findings.
2 Years
Need for systemic therapy later during disease course
Tijdsspanne: 2 Years

Stratum VI
2 Years

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

North American Consortium for Histiocytosis

Medewerkers

Histiocyte Society

Onderzoekers

  • Studie stoel: Milen Minkov, MD, Ph.D, Children's Cancer Research Institute / St. Anna Children's Hospital
  • Studie stoel: Carlos Rodriguez-Galindo, MD, North American Consortium for Histiocytosis

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

2 november 2016

Primaire voltooiing (Geschat)

1 november 2031

Studie voltooiing (Geschat)

1 november 2031

Studieregistratiedata

Eerst ingediend

7 juli 2014

Eerst ingediend dat voldeed aan de QC-criteria

30 juli 2014

Eerst geplaatst (Geschat)

31 juli 2014

Updates van studierecords

Laatste update geplaatst (Werkelijk)

10 november 2026

Laatste update ingediend die voldeed aan QC-criteria

9 november 2026

Laatst geverifieerd

1 november 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 13-428
  • 2011-001699-20 (EudraCT-nummer)
  • 042011 (Andere identificatie: Children's Cancer Research Institute)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren