Ignite Creation Date:
2024-05-05 @ 4:39 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00281983
Status:
COMPLETED
Last Update Posted:
2017-07-24
First Post:
2006-01-24
Brief Title:
Fludarabine and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Lymphocytic Leukemia or Waldenstroms Macroglobulinemia
Sponsor:
German CLL Study Group
Organization:
German CLL Study Group
Study Overview
Official Title:
Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia
Status:
COMPLETED
Status Verified Date:
2007-04
Last Known Status:
None
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 Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells It also helps stop the patients immune system from rejecting the donors stem cells Also monoclonal antibodies such as alemtuzumab can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells red blood cells white blood cells and platelets Sometimes the transplanted cells from a donor can make an immune response against the bodys normal cells Giving methotrexate cyclosporine and mycophenolate mofetil after the transplant may stop this from happening Once the donated stem cells begin working the patients immune system may see the remaining cancer cells as not belonging in the patients body and destroy them called graft-versus-tumor effect Giving an infusion of the donors white blood cells donor lymphocyte infusion may boost this effect
PURPOSE This phase III trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenströms macroglobulinemia
PURPOSE This phase III trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenströms macroglobulinemia
Detailed Description:
OBJECTIVES
Primary
Determine the feasibility and safety of induction therapy comprising fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation in patients with high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma Waldenstroms macroglobulinemia
Secondary
Determine the incidence and kinetics of clinical and molecular remissions in patients treated with this regimen
Determine event-free and overall survival of patients treated with this regimen
Determine the duration of clinical and molecular remission in relation to the underlying cytogenetic deviation in patients treated with this regimen
Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients treated with this regimen
OUTLINE This is a multicenter open-label nonrandomized pilot study
Cytoreductive therapy Patients receive up to 3 courses of cytoreductive therapy comprising fludarabine IV and cyclophosphamide IV on days 1-3 with or without rituximab IV on day 1 Patients refractory to fludarabine-containing therapy may receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for cytoreduction
Conditioning regimen Patients receive 1 of the following conditioning regimens
NOTE Patients who did not achieve partial response after cytoreductive therapy receive regimen 3
Regimen 1 Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3 If stem cells are collected from an unrelated donor patients also receive anti-thymocyte globulin ATG IV on days -4 to -1
Regimen 2 Patients undergo total-body irradiation on day -9 Patients then receive alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6 to -2
Regimen 3 Patients receive fludarabine IV on days -7 to -3 busulfan IV or orally on days -7 to -5 and cyclophosphamide IV on days -3 to -2 If stem cells are collected from an unrelated donor patients also receive ATG on days -3 to -1
Allogeneic peripheral blood stem cell transplantation PBSCT Patients undergo allogeneic PBSCT on day 0 Patients receive filgrastim G-CSF subcutaneously daily starting on day 5 and continuing until blood count recover
Graft-versus-host-disease GVHD prophylaxis Patients receive cyclosporine IV beginning on day -1 and continuing until approximately day 100 Patients treated with conditioning regimen 1 or 3 also receive methotrexate IV on days 1 3 and 6 OR oral mycophenolate mofetil twice daily on days 0-50 Patients with evidence of residual disease at least 4 weeks after completion of cyclosporine undergo donor lymphocyte infusion DLI
DLI The donor T-lymphocytes are collected from the PBSCT donor without prior G-CSF mobilization Patients receive DLI every 8 weeks in the presence of residual disease and the absence of GVHD
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 70 patients will be accrued for this study
Primary
Determine the feasibility and safety of induction therapy comprising fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation in patients with high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma Waldenstroms macroglobulinemia
Secondary
Determine the incidence and kinetics of clinical and molecular remissions in patients treated with this regimen
Determine event-free and overall survival of patients treated with this regimen
Determine the duration of clinical and molecular remission in relation to the underlying cytogenetic deviation in patients treated with this regimen
Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients treated with this regimen
OUTLINE This is a multicenter open-label nonrandomized pilot study
Cytoreductive therapy Patients receive up to 3 courses of cytoreductive therapy comprising fludarabine IV and cyclophosphamide IV on days 1-3 with or without rituximab IV on day 1 Patients refractory to fludarabine-containing therapy may receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for cytoreduction
Conditioning regimen Patients receive 1 of the following conditioning regimens
NOTE Patients who did not achieve partial response after cytoreductive therapy receive regimen 3
Regimen 1 Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3 If stem cells are collected from an unrelated donor patients also receive anti-thymocyte globulin ATG IV on days -4 to -1
Regimen 2 Patients undergo total-body irradiation on day -9 Patients then receive alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6 to -2
Regimen 3 Patients receive fludarabine IV on days -7 to -3 busulfan IV or orally on days -7 to -5 and cyclophosphamide IV on days -3 to -2 If stem cells are collected from an unrelated donor patients also receive ATG on days -3 to -1
Allogeneic peripheral blood stem cell transplantation PBSCT Patients undergo allogeneic PBSCT on day 0 Patients receive filgrastim G-CSF subcutaneously daily starting on day 5 and continuing until blood count recover
Graft-versus-host-disease GVHD prophylaxis Patients receive cyclosporine IV beginning on day -1 and continuing until approximately day 100 Patients treated with conditioning regimen 1 or 3 also receive methotrexate IV on days 1 3 and 6 OR oral mycophenolate mofetil twice daily on days 0-50 Patients with evidence of residual disease at least 4 weeks after completion of cyclosporine undergo donor lymphocyte infusion DLI
DLI The donor T-lymphocytes are collected from the PBSCT donor without prior G-CSF mobilization Patients receive DLI every 8 weeks in the presence of residual disease and the absence of GVHD
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 70 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MEDAC-FLUD10CLL | None | None | None |
| EU-20554 | None | None | None |