Clinical Trial: LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis
Brief Summary: The LCH-IV is an international, multicenter, prospective clinical study for pediatric Langerhans Cell Histiocytosis LCH (age < 18 years).
Detailed Summary:
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 previ
Sponsor: North American Consortium for Histiocytosis
Current Primary Outcome:
- Percentage of Patients with Reactivation Free Survival [ Time Frame: 12 Months ]Stratum I, II, VI
- Response Rate of Second Cycle [ Time Frame: 9 weeks ]Stratum III
- Overall and disease free survival at 1 and 3 years after reduced intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT) [ Time Frame: 3 Years ]Stratum IV
- 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 [ Time Frame: 2 Years ]Stratum V
- The time interval and cumulative incidence of progression of radiological neurodegeneration to clinically manifested ND-CNS-LCH [ Time Frame: 2 Years ]Stratum V
- Cumulative incidence of specific Permanent Consequences e.g. diabetes insipidus (DI), growth hormone deficiency (GHD), neuropsychological impairment, etc. [ Time Frame: 2 Years ]From all treatment stratum via long-term follow up in Stratum VII
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Overall Survival [ Time Frame: 2 Years ]Stratum I
- Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: 2 Years ]
- Incidence of Permanent Consequences [ Time Frame: 2 Years ]All Stratum
- Cumulative incidence of reactivations in risk organs [ Time Frame: 2 Years ]
- Time to complete disease resolution [ Time Frame: 2 Years ]Stratum III
- Response rate to the combination of prednisone, vincristine and cytarabine [ Time Frame: 2 years ]Stratum II
- The proportion of patients alive and free of disease without permanent consequences (e.g. diabetes insipidus, anterior pituitary dysfunction, radiological or clinical neurodegeneration) [ Time Frame: 2 Years ]Stratum II
- Percentage of treatment-related toxicities [ Time Frame: 2 Years ]Stratum II
- Reactivation rates after continuation treatment with Indomethacin vs. 6-MP/MTX. [ Time Frame: 2 years ]Stratum II
- The type of subsequent intensive and/or maintenance therapy utilized [ Time Frame: 2 Years ]Stratum III
- Early and late mortality [ Time Frame: 2 Years ]Stratum II
- Early and late toxicity [ Time Frame: 2 Years ]Stratum III
- d+100 transplant related mortality [ Time Frame: 2 Years ]Stratum IV
- Incidence of hematopoietic recovery, and donor chimerism at d+100 and 1 year post RIC-HSCT [ Time Frame: 2 Years ]
- Record all occurrence of skin, GI or liver abnormalities fulfilling criteria of Grades II-IV acute GVHD [ Time Frame: 2 Years ]Stratum IV: Hematopoetic Stem Cell Transplantation for Risk LCH
- Percentage of Participants with incidence of chronic GVHD [ Time Frame: 2 Years ]Stratum IV
- Response Rate to ND-CNS-targeted therapy at 12 and 24 months after start of therapy [ Time Frame: 2 years ]Stratum V
- Response of isolated tumorous CNS-LCH to 2-CDA [ Time Frame: 2 Years ]Stratum V
- Frequency of ND-CNS-LCH in patients with isolated tumorous CNS-LCH [ Time Frame: 2 Years ]Stratum V
- Methods of early identification of ND-CNS-LCH [ Time Frame: 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.
- Need for systemic therapy later during disease course [ Time Frame: 2 Years ]Stratum VI
- Identify possible risk factors for permanent consequences (PC) [ Time Frame: 2 Years ]
Original Secondary Outcome:
- Overall Survival [ Time Frame: 2 Years ]Stratum I
- Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: 2 Years ]
- Incidence of Permanent Consequences [ Time Frame: 2 Years ]All Stratum
- Cumulative incidence of reactivations in risk organs [ Time Frame: 2 Years ]
- Time to complete disease resolution [ Time Frame: 2 Years ]Stratum III
- Response rate to the combination of prednisone, vincristine and cytarabine [ Time Frame: 2 years ]Stratum II
- The proportion of patients alive and free of disease without permanent consequences (e.g. diabetes insipidus, anterior pituitary dysfunction, radiological or clinical neurodegeneration) [ Time Frame: 2 Years ]Stratum II
- Percentage of treatment-related toxicities [ Time Frame: 2 Years ]Stratum II
- Reactivation rates after continuation treatment with Indomethacin vs. 6-MP/MTX. [ Time Frame: 2 years ]Stratum II
- The type of subsequent intensive and/or maintenance therapy utilized [ Time Frame: 2 Years ]Stratum III
- Early and late mortality [ Time Frame: 2 Years ]Stratum II
- Early and late toxicity [ Time Frame: 2 Years ]Stratum III
- d+100 transplant related mortality [ Time Frame: 2 Years ]Stratum IV
- Incidence of hematopoietic recovery, and donor chimerism at d+100 and 1 year post RIC-HSCT [ Time Frame: 2 Years ]
- Record all occurance of skin, GI or liver abnormalities fulfilling criteria of Grades II-IV acute GVHD [ Time Frame: 2 Years ]Stratum IV: Hematopoetic Stem Cell Transplantation for Risk LCH
- Percentage of Participants with incidence of chronic GVHD [ Time Frame: 2 Years ]Stratum IV
- Response Rate to ND-CNS-targeted therapy at 12 and 24 months after start of therapy [ Time Frame: 2 years ]Stratum V
- Response of isolated tumorous CNS-LCH to 2-CDA [ Time Frame: 2 Years ]Stratum V
- Frequency of ND-CNS-LCH in patients with isolated tumorous CNS-LCH [ Time Frame: 2 Years ]Stratum V
- Methods of early identification of ND-CNS-LCH [ Time Frame: 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.
- Need for systemic therapy later during disease course [ Time Frame: 2 Years ]Stratum VI
- Identify possible risk factors for permanent consequences (PC) [ Time Frame: 2 Years ]
Information By: North American Consortium for Histiocytosis
Dates:
Date Received: July 7, 2014
Date Started: July 2014
Date Completion: July 2023
Last Updated: November 17, 2016
Last Verified: October 2016
- Percentage of Patients with Reactivation Free Survival [ Time Frame: 12 Months ]
