Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00051311
Status:
COMPLETED
Last Update Posted:
2021-09-09
First Post:
2003-01-08
Brief Title:
Modified Stem Cell Transplant Procedure to Treat Patients With Blood and Immune System Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of EPOCH-FR Induction Chemotherapy and Reduced-Intensity HLA-Matched Related Allogeneic Hematopoietic Stem Cell Transplantation With Cyclosporine Methotrexate GVHD Prophylaxis for Refractory or Relapsed Hematologic Malignancies
Status:
COMPLETED
Status Verified Date:
2021-08
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:
This study will investigate the safety and effectiveness of a modified stem cell transplant procedure for treating cancers of the blood and immune system Patients with cancers and pre-cancerous conditions originating in blood or immune system cells can sometimes benefit greatly from and even be cured by transplants of stem cells cells produced by the bone marrow that mature into blood cells In addition to producing new bone marrow and restoring normal blood production and immunity the donated cells fight any residual tumor cells that might have remained in the body in what is called a graft-versus-tumor effect
However severe problems and sometimes death may follow these transplants as a result of the high-dose chemotherapy and radiation that accompany the procedure Also donated immune system cells called T cells sometimes attack healthy tissues in a reaction called graft-versus-host-disease GVHD damaging organs such as the liver intestines and skin This study will use the following strategies to try to reduce these risks
induction chemotherapy to reduce patients immunity in an attempt to prevent rejection of the donated stem cells
reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression
donation of immune cells called T helper type 2 Th2 cells instead of T cells to try to reduce the risk of serious GVHD
treatment with methotrexate and cyclosporine to try to reduce the risk of serious GVHD
Patients between 12 and 75 years of age with non-Hodgkins lymphoma Hodgkins lymphoma multiple myeloma chronic lymphocytic leukemia chronic myelogenous leukemia acute myelogenous leukemia acute lymphocytic leukemia myelodysplasia idiopathic myelofibrosis polycythemia vera or chronic myelomonocytic leukemia may be eligible for this study Candidates will have a medical history physical and dental examinations blood and urine tests including a blood test for genetic match with the donor lung and heart function tests and X-ray studies A bone marrow biopsy may be done to evaluate disease status Patients with lymphoma may have a nuclear medicine test called a positron emission tomography PET scan
Participants will have a central venous line large plastic tube placed into a major vein This tube can stay in the body and be used during the entire treatment period to deliver the donated stem cells and give medications including chemotherapy and other drugs antibiotics and blood transfusions and to withdraw blood samples Treatment will start with induction chemotherapy which will include the drugs fludarabine cyclophosphamide etoposide doxorubicin vincristine and prednisone Some patients may also receive an antibody called rituximab Patients will receive one to three cycles of this treatment depending on their response to the drugs One cycle consists of 5 days on drug therapy followed by a 16-day rest period Several days before the transplant procedure patients will start conditioning chemotherapy with cyclophosphamide and fludarabine Three days after the conditioning therapy is completed the stem cells will be infused To help prevent GVHD patients will take four doses of methotrexate by vein shortly after the transplant and cyclosporine by mouth or by vein for about 6 months after the transplant
The average hospital stay for stem cell transplantation is 3 to 4 weeks After discharge patients will return for frequent follow-up visits for 3 months Monthly visits will be scheduled for the next 3 months then every 3 months for the next 18 months and less frequently for a total of at least 5 years post-transplant These visits will include bone marrow aspirates and biopsies blood draws and other tests to monitor disease status
However severe problems and sometimes death may follow these transplants as a result of the high-dose chemotherapy and radiation that accompany the procedure Also donated immune system cells called T cells sometimes attack healthy tissues in a reaction called graft-versus-host-disease GVHD damaging organs such as the liver intestines and skin This study will use the following strategies to try to reduce these risks
induction chemotherapy to reduce patients immunity in an attempt to prevent rejection of the donated stem cells
reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression
donation of immune cells called T helper type 2 Th2 cells instead of T cells to try to reduce the risk of serious GVHD
treatment with methotrexate and cyclosporine to try to reduce the risk of serious GVHD
Patients between 12 and 75 years of age with non-Hodgkins lymphoma Hodgkins lymphoma multiple myeloma chronic lymphocytic leukemia chronic myelogenous leukemia acute myelogenous leukemia acute lymphocytic leukemia myelodysplasia idiopathic myelofibrosis polycythemia vera or chronic myelomonocytic leukemia may be eligible for this study Candidates will have a medical history physical and dental examinations blood and urine tests including a blood test for genetic match with the donor lung and heart function tests and X-ray studies A bone marrow biopsy may be done to evaluate disease status Patients with lymphoma may have a nuclear medicine test called a positron emission tomography PET scan
Participants will have a central venous line large plastic tube placed into a major vein This tube can stay in the body and be used during the entire treatment period to deliver the donated stem cells and give medications including chemotherapy and other drugs antibiotics and blood transfusions and to withdraw blood samples Treatment will start with induction chemotherapy which will include the drugs fludarabine cyclophosphamide etoposide doxorubicin vincristine and prednisone Some patients may also receive an antibody called rituximab Patients will receive one to three cycles of this treatment depending on their response to the drugs One cycle consists of 5 days on drug therapy followed by a 16-day rest period Several days before the transplant procedure patients will start conditioning chemotherapy with cyclophosphamide and fludarabine Three days after the conditioning therapy is completed the stem cells will be infused To help prevent GVHD patients will take four doses of methotrexate by vein shortly after the transplant and cyclosporine by mouth or by vein for about 6 months after the transplant
The average hospital stay for stem cell transplantation is 3 to 4 weeks After discharge patients will return for frequent follow-up visits for 3 months Monthly visits will be scheduled for the next 3 months then every 3 months for the next 18 months and less frequently for a total of at least 5 years post-transplant These visits will include bone marrow aspirates and biopsies blood draws and other tests to monitor disease status
Detailed Description:
Allogeneic hematopoietic stem cell transplantation HSCT is potentially curative for refractory hematologic malignancies but its application has been limited historically by morbidity and mortality from conventional transplant preparative regimens and graft-versus-host disease GVHD Donor T cells mediate GVHD and also help to eradicate malignancies through an immune-dependent graft-versus-tumor effect Efforts to decrease preparative regimen toxicity have led to reduced-intensity or nonmyeloablative regimens facilitating the study of allogeneic HSCT in a broader population As a promising strategy for reducing GVHD donor T helper type 2 Th2 cells were shown to abrogate T helper type 1 Th1-mediated GVHD without impairing engraftment in murine models of allogeneic HSCT These findings led to a phase III clinical study of donor Th2 cells for the prevention of GVHD during reduced-intensity allogeneic HSCT CC 99-C-0143 preliminary results suggest that a randomized trial will be necessary to evaluate donor Th2 cells further
In CC 99-C-0143 a novel induction chemotherapy regimen etoposide phosphate prednisone vincristine sulfate cyclophosphamide and doxorubicin hydrochloride EPOCH-Fludarabine EPOCH-F was well tolerated and effective for sequential host immune depletion However a significant proportion of patients failed to achieve satisfactory disease control before transplant providing a basis for intensifying this induction regimen Furthermore the initial 20 patients treated on this study experienced relatively high rates of acute GVHD and considerable morbidity associated with cyclosporine monotherapy for GVHD prevention indicating that future studies should use more aggressive prophylaxis These observations warrant modifying our approach to allogeneic HSCT before undertaking a randomized study of donor Th2 cells
We now propose a pilot study of human leukocyte antigens HLA-matched related reduced-intensity allogeneic HSCT in refractory hematologic malignancies using an intensified etoposide vincristine doxorubicin prednisone cyclophosphamide and fludarabine EPOCH-F induction chemotherapy regimen with rituximab added for patients with cluster of differentiation 20 CD20 malignancies fludarabine etoposide prednisone vincristine cyclophosphamide and doxorubicin plus with or without rituximab DA-EPOCH-FR This regimen will be evaluated for toxicity and disease control before transplantation GVHD prophylaxis will consist of a standard dual-agent regimen cyclosporinemethotrexate the impact of this change on hematopoietic recovery donorrecipient chimerism and the incidence of acute GVHD will be assessed
Immune reconstitution following allogeneic HSCT is an important research interest among Experimental Transplantation and Immunology Branch Investigators Current evidence suggests a critical role for interleukin-7 IL-7 in cluster of differentiation 4 CD4 T cell homeostasis and interleukin-15 IL-15 appears crucial to cluster of differentiation 8 CD8 T cell and NK cell homeostasis The relationships between these cytokines and lymphocyte subpopulations have not been studied in the setting of allogeneic HSCT such analysis may enhance our understanding of engraftment kinetics graft-versus-host disease and immune reconstitution We will correlate serum IL-7 and IL-15 levels with changes in circulating T-cell and natural killer NK-cell subpopulations during EPOCH-FR induction chemotherapy after transplantation and with the development of GVHD
In CC 99-C-0143 a novel induction chemotherapy regimen etoposide phosphate prednisone vincristine sulfate cyclophosphamide and doxorubicin hydrochloride EPOCH-Fludarabine EPOCH-F was well tolerated and effective for sequential host immune depletion However a significant proportion of patients failed to achieve satisfactory disease control before transplant providing a basis for intensifying this induction regimen Furthermore the initial 20 patients treated on this study experienced relatively high rates of acute GVHD and considerable morbidity associated with cyclosporine monotherapy for GVHD prevention indicating that future studies should use more aggressive prophylaxis These observations warrant modifying our approach to allogeneic HSCT before undertaking a randomized study of donor Th2 cells
We now propose a pilot study of human leukocyte antigens HLA-matched related reduced-intensity allogeneic HSCT in refractory hematologic malignancies using an intensified etoposide vincristine doxorubicin prednisone cyclophosphamide and fludarabine EPOCH-F induction chemotherapy regimen with rituximab added for patients with cluster of differentiation 20 CD20 malignancies fludarabine etoposide prednisone vincristine cyclophosphamide and doxorubicin plus with or without rituximab DA-EPOCH-FR This regimen will be evaluated for toxicity and disease control before transplantation GVHD prophylaxis will consist of a standard dual-agent regimen cyclosporinemethotrexate the impact of this change on hematopoietic recovery donorrecipient chimerism and the incidence of acute GVHD will be assessed
Immune reconstitution following allogeneic HSCT is an important research interest among Experimental Transplantation and Immunology Branch Investigators Current evidence suggests a critical role for interleukin-7 IL-7 in cluster of differentiation 4 CD4 T cell homeostasis and interleukin-15 IL-15 appears crucial to cluster of differentiation 8 CD8 T cell and NK cell homeostasis The relationships between these cytokines and lymphocyte subpopulations have not been studied in the setting of allogeneic HSCT such analysis may enhance our understanding of engraftment kinetics graft-versus-host disease and immune reconstitution We will correlate serum IL-7 and IL-15 levels with changes in circulating T-cell and natural killer NK-cell subpopulations during EPOCH-FR induction chemotherapy after transplantation and with the development of GVHD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| 03-C-0077 | None | None | None |