Combination Chemotherapy Followed By Donor Stem Cell Transplant in Treating Patients With Hemophagocytic Lymphohistiocytosis
NCT ID: NCT00334672
Last Updated: 2013-09-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
288 participants
INTERVENTIONAL
2006-03-31
Brief Summary
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PURPOSE: This phase III trial is studying how well combination chemotherapy followed by a donor stem cell transplant works in treating patients with hemophagocytic lymphohistiocytosis.
Detailed Description
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Primary
* Provide and evaluate revised induction and maintenance therapy comprising etoposide, dexamethasone, and cyclosporine, in terms of achieving and maintaining an acceptable clinical condition in order to perform a curative allogeneic hematopoietic stem cell transplantation (AHSCT), in patients with primary inherited or severe and persistent secondary hemophagocytic lymphohistiocytosis (HLH).
* Evaluate and improve the outcome of AHSCT with various types of donors.
* Determine the prognostic importance of the state of remission at the time of AHSCT.
* Evaluate the neurological complications, in terms of early neurological alterations and cerebrospinal fluid (CSF) findings, in patients treated with this regimen.
Secondary
* Improve the understanding of the pathophysiology of HLH by conducting biological studies of genetics and cytotoxicity in these patients, including genotype-phenotype studies and the prognostic value of natural killer (NK) cell activity subtyping.
OUTLINE: This is a multicenter study.
* Induction therapy (weeks 1-8): Patients receive etoposide IV over 1-3 hours twice weekly in weeks 1 and 2 and then once weekly in weeks 3-8. Patients also receive dexamethasone IV or orally once daily and cyclosporine IV or orally twice daily in weeks 1-8. Patients with clinically evident, progressive neurological symptoms or an abnormal cerebrospinal fluid (CSF) (cell count and protein) that has not improved after 2 weeks of induction therapy undergo intrathecal therapy comprising methotrexate and hydrocortisone once weekly in weeks 3-6.
Patients are evaluated after 8 weeks of induction therapy. Patients with primary (i.e., familial) hemophagocytic lymphohistiocytosis (HLH) or genetic evidence of HLH proceed to maintenance therapy. Patients with severe and persistent secondary (i.e., nonfamilial) HLH and no genetic evidence of HLH proceed to maintenance therapy only if their disease is still active after induction therapy. Patients with nonfamilial HLH and no genetic evidence of HLH who have achieved complete remission (CR) discontinue treatment. If their disease reactivates, they may then proceed to allogeneic hematopoietic stem cell transplantation (AHSCT).
* Maintenance therapy (weeks 9-40): Patients receive dexamethasone IV on days 1-3 in weeks 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, and 40; etoposide IV over 1-3 hours once in weeks 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, and 39; and cyclosporine IV or orally twice daily in weeks 9-40.
After completion of maintenance therapy, patients with primary (i.e., familial) HLH, severe and persistent secondary (i.e., nonfamilial) HLH, or reactivating disease proceed to AHSCT. Patients with nonfamilial HLH who have completed maintenance therapy, but do not go on to receive AHSCT, may be recommended for additional maintenance therapy at the discretion of the treating physician.
* AHSCT:
* Preparative regimen: Patients receive a preparative regimen comprising busulfan orally or IV four times daily on days -8 to -5, etoposide IV over 6 hours on day -4, and cyclophosphamide IV over 1 hour on days -3 and -2. Patients who are undergoing unrelated AHSCT, also receive antithymocyte globulin (ATG) IV over 12 hours on days -3 to -1.
* Transplantation: Patients undergo AHSCT on day 0.
* Graft-versus-host disease prophylaxis: Beginning on day -1, patients receive cyclosporine IV continuously and then orally, when tolerated, once daily for 6-12 months. Patients also receive methotrexate\* IV on days 1, 3, and 6.
NOTE: \*As a substitute for methotrexate, patients may receive oral mycophenolate mofetil twice daily on days 0-40, followed by a taper and discontinuation.
Patients undergo periodic blood collection and bone marrow biopsies for biological studies.
After completion of study treatment, patients are followed periodically for up to 5 years.
PROJECTED ACCRUAL: A total of 288 patients will be accrued for this study.
Conditions
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Keywords
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Study Design
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TREATMENT
NONE
Interventions
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anti-thymocyte globulin
busulfan
cyclophosphamide
cyclosporine
dexamethasone
etoposide
methotrexate
mycophenolate mofetil
therapeutic hydrocortisone
laboratory biomarker analysis
allogeneic hematopoietic stem cell transplantation
biopsy
Eligibility Criteria
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Inclusion Criteria
* Acceptable donor meeting 1 of the following criteria:
* HLA-identical related donor
* Matched unrelated donor
* Mismatched unrelated donor
* Familial haploidentical donor
PATIENT CHARACTERISTICS:
* Not specified
PRIOR CONCURRENT THERAPY:
* No prior cytotoxic treatment for HLH
* No prior cyclosporine treatment for HLH
17 Years
ALL
No
Sponsors
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Children's Cancer and Leukaemia Group
OTHER
Principal Investigators
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Vasanta Nanduri, MD
Role: STUDY_CHAIR
Watford General Hospital
Locations
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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
Watford General Hospital
Herts, England, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, 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 Manchester Children's Hospital
Manchester, England, United Kingdom
Children's Hospital - Sheffield
Sheffield, England, United Kingdom
Southampton General Hospital
Southampton, England, United Kingdom
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom
Countries
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Other Identifiers
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CCLG-LCH-2006-02
Identifier Type: -
Identifier Source: secondary_id
EU-20619
Identifier Type: -
Identifier Source: secondary_id
UKCCSG-HLH-2004
Identifier Type: -
Identifier Source: secondary_id
EUDRACT-2005-002187-28
Identifier Type: -
Identifier Source: secondary_id
CDR0000481605
Identifier Type: -
Identifier Source: org_study_id