Combination Chemotherapy Followed By Donor Stem Cell Transplant in Treating Patients With Hemophagocytic Lymphohistiocytosis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00334672|
Recruitment Status : Unknown
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was: Active, not recruiting
First Posted : June 8, 2006
Last Update Posted : September 17, 2013
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of hemophagocytic lymphohistiocytosis cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more hemophagocytic lymphohistiocytosis cells. A donor stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Cyclosporine and methotrexate may stop this from happening.
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.
|Condition or disease||Intervention/treatment||Phase|
|Nonneoplastic Condition||Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: dexamethasone Drug: etoposide Drug: methotrexate Drug: mycophenolate mofetil Drug: therapeutic hydrocortisone Other: laboratory biomarker analysis Procedure: allogeneic hematopoietic stem cell transplantation Procedure: biopsy||Phase 3|
Hide Detailed Description
- 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.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||288 participants|
|Masking:||None (Open Label)|
|Official Title:||Hemophagocytic Lymphohistiocytosis|
|Study Start Date :||March 2006|
|Estimated Primary Completion Date :||November 2010|
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00334672
|Birmingham Children's Hospital|
|Birmingham, England, United Kingdom, B4 6NH|
|Institute of Child Health at University of Bristol|
|Bristol, England, United Kingdom, BS2 8AE|
|Cambridge, England, United Kingdom, CB2 2QQ|
|Watford General Hospital|
|Herts, England, United Kingdom, WD18 0HB|
|Leeds Cancer Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS9 7TF|
|Royal Liverpool Children's Hospital, Alder Hey|
|Liverpool, England, United Kingdom, L12 2AP|
|Great Ormond Street Hospital for Children|
|London, England, United Kingdom, WC1N 3JH|
|Royal Manchester Children's Hospital|
|Manchester, England, United Kingdom, M27 4HA|
|Children's Hospital - Sheffield|
|Sheffield, England, United Kingdom, S10 2TH|
|Southampton General Hospital|
|Southampton, England, United Kingdom, SO16 6YD|
|Royal Aberdeen Children's Hospital|
|Aberdeen, Scotland, United Kingdom, AB25 2ZG|
|Royal Hospital for Sick Children|
|Edinburgh, Scotland, United Kingdom, EH9 1LF|
|Royal Hospital for Sick Children|
|Glasgow, Scotland, United Kingdom, G3 8SJ|
|Study Chair:||Vasanta Nanduri, MD||Watford General Hospital|