LCH-IV International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis

  • STATUS
    Recruiting
  • participants needed
    1100
  • sponsor
    North American Consortium for Histiocytosis
Updated on 8 November 2020
Investigator
Stephan Ladisch, MD
Primary Contact
Children's National Medical Center (5.4 mi away) Contact
+8 other location

Summary

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

Description

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)

Details
Treatment methotrexate, prednisone, Mercaptopurine, indomethacin, cytosine arabinoside, Intravenous immunoglobulin, Vinblastine, 2-chlorodeoxyadenosine, hematopoietic stem cell transplantation (RIC-HSCT)
Clinical Study IdentifierNCT02205762
SponsorNorth American Consortium for Histiocytosis
Last Modified on8 November 2020

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Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age less than or equal to 18 yrs?
Gender: Male or Female
Do you have langerhans cell histiocytosis?
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/L) 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)
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