Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00047060
Status:
COMPLETED
Last Update Posted:
2023-11-14
First Post:
2002-10-03
Brief Title:
Stem Cell Transplant Therapy With Campath-1H for Treating Advanced Mycosis Fungoides and Sezary Syndrome
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Study of HLA-matched Mobilized Peripheral Blood Hematopoietic Stem Cell Transplantation for Advanced Mycosis FungoidesSezary Syndrome Using Nonmyeloablative Conditioning With Campath-1H
Status:
COMPLETED
Status Verified Date:
2019-02-13
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 donor stem cell transplantation procedure for treating advanced mycosis fungoides MF a lymphoma primarily affecting the skin and Sezary syndrome SS a leukemic form of the disease Donated stem cells cells produced by the bone marrow that mature into the different blood components white cells red cells and platelets can cure patients with certain leukemias and lymphomas and multiple myeloma These cells generate a completely new functioning bone marrow In addition immune cells from the donor grow and generate a new immune system to help fight infections The new immune cells also attack any residual tumor cells left in the body after intensive chemotherapy However stem cell transplantation carries a significant risk of death because it requires completely suppressing the immune system with high-dose chemotherapy and radiation In addition lymphocytes from the donor may cause what is called graft vs host disease GvHD in which these cells see the patient s cells as foreign and mount an immune response to destroy them To try to reduce these risks patients in this study will be given low-dose chemotherapy and no radiation a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression In addition a monoclonal antibody called Campath-1H will be given to target lymphocytes including those that have become cancerous
Patients with advanced MF or SS who are between 18 and 70 years of age and have a matched family donor 18 years of age or older may be eligible for this study Candidates will have a medical history physical examination and blood tests lung and heart function tests X-rays of the chest eye examination and bone marrow sampling withdrawal through a needle of about a tablespoon of marrow from the hip bone and small skin biopsy surgical removal of a piece of tissue for microscopic examination or needle biopsy of the tumor
Stem cells will be collected from both the patient and donor To do this the hormone G-CSF will be injected under the skin for several days to push stem cells out of the bone marrow into the bloodstream Then the stem cells will be collected by apheresis In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the required cells are separated out and removed The rest of the blood is returned through a needle in the other arm
Before the transplant a central venous line large plastic tube is placed into a major vein This tube can stay in the body and be used the entire treatment period to deliver the donated stem cells give medications transfuse blood if needed and withdraw blood samples Several days before the transplant procedure patients will start a conditioning regimen of low-dose chemotherapy with Campath 1H fludarabine and if necessary cyclophosphamide When the conditioning therapy is completed the stem cells will be infused over a period of up to 4 hours To help prevent rejection of donor cells and GvHD cyclosporine and mycophenolate mofetil will be given by mouth or by vein for about 3 months starting 4 days before the transplantation
The anticipated hospital stay is 3 to 4 days when the first 3 doses of Campath will be monitored for drug side effects The rest of the procedures including the transplant can be done on an outpatient basis Follow-up visits for the first 3 months after the transplant will be scheduled once or twice a week for a physical examination blood tests and symptoms check Then visits will be scheduled at 6 12 18 24 30 36 and 48 months post-transplant Visits for the first 3 years will include blood tests skin biopsies and bone marrow biopsies
Patients with advanced MF or SS who are between 18 and 70 years of age and have a matched family donor 18 years of age or older may be eligible for this study Candidates will have a medical history physical examination and blood tests lung and heart function tests X-rays of the chest eye examination and bone marrow sampling withdrawal through a needle of about a tablespoon of marrow from the hip bone and small skin biopsy surgical removal of a piece of tissue for microscopic examination or needle biopsy of the tumor
Stem cells will be collected from both the patient and donor To do this the hormone G-CSF will be injected under the skin for several days to push stem cells out of the bone marrow into the bloodstream Then the stem cells will be collected by apheresis In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the required cells are separated out and removed The rest of the blood is returned through a needle in the other arm
Before the transplant a central venous line large plastic tube is placed into a major vein This tube can stay in the body and be used the entire treatment period to deliver the donated stem cells give medications transfuse blood if needed and withdraw blood samples Several days before the transplant procedure patients will start a conditioning regimen of low-dose chemotherapy with Campath 1H fludarabine and if necessary cyclophosphamide When the conditioning therapy is completed the stem cells will be infused over a period of up to 4 hours To help prevent rejection of donor cells and GvHD cyclosporine and mycophenolate mofetil will be given by mouth or by vein for about 3 months starting 4 days before the transplantation
The anticipated hospital stay is 3 to 4 days when the first 3 doses of Campath will be monitored for drug side effects The rest of the procedures including the transplant can be done on an outpatient basis Follow-up visits for the first 3 months after the transplant will be scheduled once or twice a week for a physical examination blood tests and symptoms check Then visits will be scheduled at 6 12 18 24 30 36 and 48 months post-transplant Visits for the first 3 years will include blood tests skin biopsies and bone marrow biopsies
Detailed Description:
Primary cutaneous T-cell lymphomas CTCL are a group of lymphoproliferative disorders characterized by localization of neoplastic T cells to the skin at presentation Mycosis fungoides MF and its leukemic variant Sezary syndrome SS are the most prevalent forms of CTCL While early stage MF is restricted to patches and plaques involving the skin most patients eventually develop cutaneous tumors generalized erythroderma or dissemination to peripheral blood lymph nodes or visceral organs Currently existing therapy of tumor-stage and disseminated CTCL is palliative with most patients dying within 1-5 years The presence of CD8 cells in close proximity to dermal neoplastic infiltrates in early stages of the disease and the clinical response seen with some immunomodulatory agents suggests that CTCL may be potential targets for immunotherapy-based interventions
Allogeneic stem cell transplantation is a curative treatment modality successfully employed in a number of hematologic malignancies The curative effect of this approach is in part mediated by donor-derived T lymphocytes with reactivity for patient leukemic cells The power of this graft versus leukemia effect GVL is best illustrated in patients with relapsed Chronic Myeloid Leukemia CML after an allogeneic bone marrow transplant in whom a single donor lymphocyte infusion DLI can induce remission We hypothesize that neoplastic T cells in MFSS may similarly be susceptible to a graft vs tumor GVT effect Unfortunately advanced patient age and a 25 to 35 risk of transplant related mortality TRM preclude the use of conventional dose- intensive allogeneic peripheral blood stem cell transplantation PBSCT in patients with advanced CTCL who might otherwise benefit from this approach The risk of TRM related to conditioning can be circumvented at least partially by using a reduced-intensity conditioning regimen to prepare the patient for transplantation
In this study we will treat male and non-pregnant female subjects between the ages of 18 and 70 years both inclusive suffering from advanced MFSS with an allogeneic peripheral blood stem cell PBSC transplant from an HLA-matched family donor or an HLA matched 1010 allele level match unrelated donor A low intensity nonmyeloablative conditioning regimen employing the anti-CD52 monoclonal antibody Campath-1H alemtuzumab and fludarabine will be used to induce host immunosuppression to facilitate donor hematopoietic and lymphoid engraftment We anticipate minimal host myelosuppression and consequently reduced early transplant toxicity with this conditioning regimen Immune and hematopoietic reconstitution will be achieved by infusion of unmanipulated donor-derived granulocyte colony stimulation factor G-CSF mobilized peripheral blood stem cells Infusion of donor lymphocytes in incremental doses will be used to promote engraftment or disease regression when indicated Cyclosporine A CSA will be used as prophylaxis against graft vs host disease GVHD with dose adjustments made as necessary to favor complete donor chimerism and disease regression
A total of up to 25 subjects transplant recipients will be treated on this protocol The primary end point of this study is efficacy proportion of subjects achieving a complete response Other end points include assessment of donor-host chimerism in various hematopoietic and lymphoid cells overall response incidence of acute and chronic GVHD graft failure assessment of lymphoid subset reconstitution transplant related morbidity and mortality and disease-free and overall survival and the outcomes of transplantation by the donor type related vs unrelated
Allogeneic stem cell transplantation is a curative treatment modality successfully employed in a number of hematologic malignancies The curative effect of this approach is in part mediated by donor-derived T lymphocytes with reactivity for patient leukemic cells The power of this graft versus leukemia effect GVL is best illustrated in patients with relapsed Chronic Myeloid Leukemia CML after an allogeneic bone marrow transplant in whom a single donor lymphocyte infusion DLI can induce remission We hypothesize that neoplastic T cells in MFSS may similarly be susceptible to a graft vs tumor GVT effect Unfortunately advanced patient age and a 25 to 35 risk of transplant related mortality TRM preclude the use of conventional dose- intensive allogeneic peripheral blood stem cell transplantation PBSCT in patients with advanced CTCL who might otherwise benefit from this approach The risk of TRM related to conditioning can be circumvented at least partially by using a reduced-intensity conditioning regimen to prepare the patient for transplantation
In this study we will treat male and non-pregnant female subjects between the ages of 18 and 70 years both inclusive suffering from advanced MFSS with an allogeneic peripheral blood stem cell PBSC transplant from an HLA-matched family donor or an HLA matched 1010 allele level match unrelated donor A low intensity nonmyeloablative conditioning regimen employing the anti-CD52 monoclonal antibody Campath-1H alemtuzumab and fludarabine will be used to induce host immunosuppression to facilitate donor hematopoietic and lymphoid engraftment We anticipate minimal host myelosuppression and consequently reduced early transplant toxicity with this conditioning regimen Immune and hematopoietic reconstitution will be achieved by infusion of unmanipulated donor-derived granulocyte colony stimulation factor G-CSF mobilized peripheral blood stem cells Infusion of donor lymphocytes in incremental doses will be used to promote engraftment or disease regression when indicated Cyclosporine A CSA will be used as prophylaxis against graft vs host disease GVHD with dose adjustments made as necessary to favor complete donor chimerism and disease regression
A total of up to 25 subjects transplant recipients will be treated on this protocol The primary end point of this study is efficacy proportion of subjects achieving a complete response Other end points include assessment of donor-host chimerism in various hematopoietic and lymphoid cells overall response incidence of acute and chronic GVHD graft failure assessment of lymphoid subset reconstitution transplant related morbidity and mortality and disease-free and overall survival and the outcomes of transplantation by the donor type related vs unrelated
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 |
|---|---|---|---|
| 02-H-0250 | OTHER | NIH - National Heart Lung and Blood Institute | None |