Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00334672
Status:
UNKNOWN
Last Update Posted:
2013-09-17
First Post:
2006-06-07
Brief Title:
Combination Chemotherapy Followed By Donor Stem Cell Transplant in Treating Patients With Hemophagocytic Lymphohistiocytosis
Sponsor:
Childrens Cancer and Leukaemia Group
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Hemophagocytic Lymphohistiocytosis
Status:
UNKNOWN
Status Verified Date:
2009-06
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 bodys 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
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:
OBJECTIVES
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 ie familial hemophagocytic lymphohistiocytosis HLH or genetic evidence of HLH proceed to maintenance therapy Patients with severe and persistent secondary ie 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 ie familial HLH severe and persistent secondary ie 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
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 ie familial hemophagocytic lymphohistiocytosis HLH or genetic evidence of HLH proceed to maintenance therapy Patients with severe and persistent secondary ie 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 ie familial HLH severe and persistent secondary ie 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
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EUDRACT-2005-002187-28 | None | None | None |
| CCLG-LCH-2006-02 | None | None | None |
| EU-20619 | None | None | None |
| UKCCSG-HLH-2004 | None | None | None |