Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00080925
Status:
COMPLETED
Last Update Posted:
2012-03-08
First Post:
2004-04-07
Brief Title:
T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
T-Cell Depleted Reduced-Intensity Allogeneic Stem Cell Transplantation From Haploidentical Related Donors For Hematologic Malignancies
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Donor peripheral stem cell transplantation may be able to replace bone marrow and immune cells that were destroyed by chemotherapy Sometimes the transplanted cells from a donor are rejected by the bodys normal cells Eliminating the T cells from the donor cells before transplanting them and giving cyclosporine may prevent this from happening
PURPOSE This phase I trial is studying the side effects of T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning chemotherapy in treating patients with hematologic malignancies
PURPOSE This phase I trial is studying the side effects of T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning chemotherapy in treating patients with hematologic malignancies
Detailed Description:
OBJECTIVES
Primary
Determine engraftment in patients with hematologic malignancies treated with T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning
Secondary
Determine the incidence of acute graft-versus-host disease GVHD and nonrelapse mortality within 100 days after transplantation in these patients
Correlate levels of host immunosuppression before transplantation conditioning as evaluated by peripheral blood CD4 counts with graft rejectionfailure within 100 days after transplantation and the level of donor hematopoietic chimerism 28 days after transplantation in these patients
Correlate donor-versus-recipient natural killer cell alloreactivity with graft rejectionfailure acute GVHD and relapse of malignant disease in patients treated with this regimen
Determine the development of allospecific cytotoxic T-lymphocytes after transplantation in patients with myeloid or lymphoid leukemia
Correlate serum interleukin-7 and interleukin-15 levels with in vivo changes in host lymphocyte subpopulations in these patients during sequential immunoablative chemotherapy before allogeneic stem cell transplantation and during immune reconstitution after transplantation
OUTLINE This is a pilot study
Induction chemotherapy Patients receive 1 of 2 induction chemotherapy regimens according to diagnosis Patients with partial response or better after prior therapy ie already adequately immune depleted proceed directly to the transplantation preparative regimen
Regimen A Hodgkins lymphoma non-Hodgkins lymphoma except lymphoblastic lymphoma chronic lymphocytic leukemia prolymphocytic leukemia or multiple myeloma Patients receive rituximab IV if they have CD20 B-cell malignancies on day 1 fludarabine IV over 30 minutes on days 1-4 etoposide doxorubicin and vincristine IV continuously on days 1-4 cyclophosphamide IV over 30 minutes on day 5 oral prednisone on days 1-5 and filgrastim G-CSF subcutaneously SC beginning on day 6 and continuing until blood counts recover
Regimen B lymphoblastic lymphoma acute myeloid leukemia acute lymphoblastic leukemia refractory anemia with excess blasts myeloproliferative disorders chronic myelomonocytic leukemia or chronic myelogenous leukemia Patients receive G-CSF SC beginning 24 hours before initiating induction chemotherapy and continuing until blood counts recover Patients also receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5
For both regimens treatment repeats every 21 days for 1-2 courses Patients who achieve remission or who have responsive or stable disease after induction chemotherapy then proceed to transplantation preparative regimen chemotherapy
Transplantation preparative regimen chemotherapy Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3
Graft-versus-host disease GVHD prophylaxis Patients receive cyclosporine IV over 2 hours twice daily beginning on day -1 and continuing IV or orally until day 100 Patients with no acute GVHD at day 100 taper cyclosporine over 12 weeks
Allogeneic stem cell transplantation SCT Patients undergo T-cell-depleted allogeneic peripheral blood SCT on day 0 Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover
Donor lymphocyte infusion DLI Patients with persistent or progressive malignant disease after transplantation or mixed chimerism that does not improve after tapering or discontinuing immunosuppression therapy may receive DLI DLI may be administered alone or in combination with chemotherapy DLI repeats every 4 weeks until adequate donor chimerism is achieved or until GVHD develops
Patients are followed at 28 and 100 days and then at 6 9 12 18 and 24 months
PROJECTED ACCRUAL A total of 6-20 patients will be accrued for this study within 2 years
Primary
Determine engraftment in patients with hematologic malignancies treated with T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning
Secondary
Determine the incidence of acute graft-versus-host disease GVHD and nonrelapse mortality within 100 days after transplantation in these patients
Correlate levels of host immunosuppression before transplantation conditioning as evaluated by peripheral blood CD4 counts with graft rejectionfailure within 100 days after transplantation and the level of donor hematopoietic chimerism 28 days after transplantation in these patients
Correlate donor-versus-recipient natural killer cell alloreactivity with graft rejectionfailure acute GVHD and relapse of malignant disease in patients treated with this regimen
Determine the development of allospecific cytotoxic T-lymphocytes after transplantation in patients with myeloid or lymphoid leukemia
Correlate serum interleukin-7 and interleukin-15 levels with in vivo changes in host lymphocyte subpopulations in these patients during sequential immunoablative chemotherapy before allogeneic stem cell transplantation and during immune reconstitution after transplantation
OUTLINE This is a pilot study
Induction chemotherapy Patients receive 1 of 2 induction chemotherapy regimens according to diagnosis Patients with partial response or better after prior therapy ie already adequately immune depleted proceed directly to the transplantation preparative regimen
Regimen A Hodgkins lymphoma non-Hodgkins lymphoma except lymphoblastic lymphoma chronic lymphocytic leukemia prolymphocytic leukemia or multiple myeloma Patients receive rituximab IV if they have CD20 B-cell malignancies on day 1 fludarabine IV over 30 minutes on days 1-4 etoposide doxorubicin and vincristine IV continuously on days 1-4 cyclophosphamide IV over 30 minutes on day 5 oral prednisone on days 1-5 and filgrastim G-CSF subcutaneously SC beginning on day 6 and continuing until blood counts recover
Regimen B lymphoblastic lymphoma acute myeloid leukemia acute lymphoblastic leukemia refractory anemia with excess blasts myeloproliferative disorders chronic myelomonocytic leukemia or chronic myelogenous leukemia Patients receive G-CSF SC beginning 24 hours before initiating induction chemotherapy and continuing until blood counts recover Patients also receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5
For both regimens treatment repeats every 21 days for 1-2 courses Patients who achieve remission or who have responsive or stable disease after induction chemotherapy then proceed to transplantation preparative regimen chemotherapy
Transplantation preparative regimen chemotherapy Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3
Graft-versus-host disease GVHD prophylaxis Patients receive cyclosporine IV over 2 hours twice daily beginning on day -1 and continuing IV or orally until day 100 Patients with no acute GVHD at day 100 taper cyclosporine over 12 weeks
Allogeneic stem cell transplantation SCT Patients undergo T-cell-depleted allogeneic peripheral blood SCT on day 0 Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover
Donor lymphocyte infusion DLI Patients with persistent or progressive malignant disease after transplantation or mixed chimerism that does not improve after tapering or discontinuing immunosuppression therapy may receive DLI DLI may be administered alone or in combination with chemotherapy DLI repeats every 4 weeks until adequate donor chimerism is achieved or until GVHD develops
Patients are followed at 28 and 100 days and then at 6 9 12 18 and 24 months
PROJECTED ACCRUAL A total of 6-20 patients will be accrued for this study within 2 years
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 |
|---|---|---|---|
| CDR0000357432 | None | None | None |
| 04-C-0116 | None | None | None |