Ignite Creation Date:
2024-05-05 @ 10:23 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006413
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2000-10-17
Brief Title:
Stem Cell Transplantation to Treat Systemic Mastocytosis
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Low Intensity Preparative Regimen Followed by HLA-Matched Mobilized Peripheral Blood Stem Cell Transplantation for Systemic Mastocytosis
Status:
COMPLETED
Status Verified Date:
2006-12-14
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 an experimental stem cell transplant procedure for treating mastocytosis-a disease of abnormal mast cell growth Patients often feel faint have skin problems joint and bone pain low blood counts and enlarged liver spleen or lymph nodes As yet there is no cure for mastocytosis and treatment is aimed at controlling symptoms
Stem cells are cells produced by the bone marrow that mature into the different blood components-white cells red cells and platelets Transplantation of allogeneic donated stem cells is a mainstay of therapy for some forms of leukemia Patients first receive intensive chemotherapy and radiation to rid the body of cancer cells This conditioning is followed by transplantation of donated stem cells to generate new healthy bone marrow In addition to producing the new bone marrow the donated cells also fight any residual tumor cells that might have remained in the body This is called a graft-versus-tumor effect This study will examine whether a stem cell transplant from a healthy donor can similarly target and destroy mast cells in a graft-versus-mast cell effect Also to try to reduce the harmful side effects of chemotherapy and radiation this study will use lower dose chemotherapy and no radiation
Patients with advanced mastocytosis between 10 and 80 years old may be eligible for this study They will be
tested for HLA type matching with a sibling and will undergo a medical history physical examination and several tests to determine eligibility for the study
Participants will undergo apheresis to collect lymphocytes a type of white blood cell for immune function tests In this procedure blood is drawn through a needle in the arm similar to donating a unit of blood The lymphocytes are then separated and collected by a cell separator machine and the rest of the blood is returned through a needle in the other arm Patients will also have a central venous line flexible plastic tube placed in their upper chest leading to a vein This line will remain in place throughout the transplant and recovery period and will be used to transfuse blood components administer medicines infuse the donated stem cells and draw blood for tests Patients will begin conditioning with cyclophosphamide starting 7 days before the transplant and fludarabine starting 5 days before the transplant to prevent rejection of the donated cells From 1 to 3 days after the chemotherapy is completed the stem cells will be transfused through the central venous line Also from 4 days before the transplantation until about 3 months after the procedure patients will receive cyclosporine and mycophenolate mofetil-drugs that help prevent both rejection of the donated cells and attack by the donor cells on the patients cells called graft-versus-host disease
Patients will stay in the hospital about 20 to 30 days after the transplant After discharge they will continue to take antibiotics cyclosporine and mycophenolate mofetil at home If the mastocytosis progresses cyclosporine and mycophenolate mofetil will be tapered over 4 weeks If the mastocytosis persists patients may receive additional transfusions of donor lymphocytes to help kill the mast cells
Patients progress will be followed weekly or twice weekly for 3 months then at 6 12 18 24 30 36 48 and 60 months after transplant and then twice a year for various tests treatments and examinations
Stem cells are cells produced by the bone marrow that mature into the different blood components-white cells red cells and platelets Transplantation of allogeneic donated stem cells is a mainstay of therapy for some forms of leukemia Patients first receive intensive chemotherapy and radiation to rid the body of cancer cells This conditioning is followed by transplantation of donated stem cells to generate new healthy bone marrow In addition to producing the new bone marrow the donated cells also fight any residual tumor cells that might have remained in the body This is called a graft-versus-tumor effect This study will examine whether a stem cell transplant from a healthy donor can similarly target and destroy mast cells in a graft-versus-mast cell effect Also to try to reduce the harmful side effects of chemotherapy and radiation this study will use lower dose chemotherapy and no radiation
Patients with advanced mastocytosis between 10 and 80 years old may be eligible for this study They will be
tested for HLA type matching with a sibling and will undergo a medical history physical examination and several tests to determine eligibility for the study
Participants will undergo apheresis to collect lymphocytes a type of white blood cell for immune function tests In this procedure blood is drawn through a needle in the arm similar to donating a unit of blood The lymphocytes are then separated and collected by a cell separator machine and the rest of the blood is returned through a needle in the other arm Patients will also have a central venous line flexible plastic tube placed in their upper chest leading to a vein This line will remain in place throughout the transplant and recovery period and will be used to transfuse blood components administer medicines infuse the donated stem cells and draw blood for tests Patients will begin conditioning with cyclophosphamide starting 7 days before the transplant and fludarabine starting 5 days before the transplant to prevent rejection of the donated cells From 1 to 3 days after the chemotherapy is completed the stem cells will be transfused through the central venous line Also from 4 days before the transplantation until about 3 months after the procedure patients will receive cyclosporine and mycophenolate mofetil-drugs that help prevent both rejection of the donated cells and attack by the donor cells on the patients cells called graft-versus-host disease
Patients will stay in the hospital about 20 to 30 days after the transplant After discharge they will continue to take antibiotics cyclosporine and mycophenolate mofetil at home If the mastocytosis progresses cyclosporine and mycophenolate mofetil will be tapered over 4 weeks If the mastocytosis persists patients may receive additional transfusions of donor lymphocytes to help kill the mast cells
Patients progress will be followed weekly or twice weekly for 3 months then at 6 12 18 24 30 36 48 and 60 months after transplant and then twice a year for various tests treatments and examinations
Detailed Description:
Mastocytosis is a disease characterized by excessive numbers of mast cells in skin bone marrow and internal organs such as liver spleen and lymph nodes Its genesis appears to be related to somatic mutations in c-kit the receptor for mast cell growth factor Although most patients present with the indolent form of the disease approximately one-third of the patients have an associated hematologic disorder such as a myeloproliferative state or myelodysplastic syndrome Patients with advanced forms of the disease including those with an associated hematologic disorder have a poorer prognosis than those with indolent disease There is no treatment known to cure or improve the natural course of mastocytosis Since mast cells arise in the bone marrow from a CD34 progenitor bone marrow transplantation may offer the only hope for a cure
In this protocol we propose to treat patients with advanced forms of mastocytosis with an allogeneic stem cell transplant from an HLA-identical sibling using a low intensity non-myeloablative regimen This approach has the advantage of decreasing the transplant-related toxicity while allowing adequate immunosuppression to establish stem cell and lymphocyte engraftment Donor derived CD4 and CD8 lymphocytes which are important in killing of leukemic cells by mounting a graft versus leukemia effect should be useful in the elimination of aberrant mast cells and their progenitors that is graft-versus-mast cell effect This mechanism may be particularly relevant in mastocytosis as point mutations of c-kit may constitute an antigenically distinct T-cell target for recognition by the engrafted donor cells
The primary end point of this study is regression of mastocytosis The secondary end points are engraftment hematologic response degree of donor-host chimerism incidence and severity of acute and chronic GVHD transplant related morbidity and mortality relapse disease free survival and overall survival
In this protocol we propose to treat patients with advanced forms of mastocytosis with an allogeneic stem cell transplant from an HLA-identical sibling using a low intensity non-myeloablative regimen This approach has the advantage of decreasing the transplant-related toxicity while allowing adequate immunosuppression to establish stem cell and lymphocyte engraftment Donor derived CD4 and CD8 lymphocytes which are important in killing of leukemic cells by mounting a graft versus leukemia effect should be useful in the elimination of aberrant mast cells and their progenitors that is graft-versus-mast cell effect This mechanism may be particularly relevant in mastocytosis as point mutations of c-kit may constitute an antigenically distinct T-cell target for recognition by the engrafted donor cells
The primary end point of this study is regression of mastocytosis The secondary end points are engraftment hematologic response degree of donor-host chimerism incidence and severity of acute and chronic GVHD transplant related morbidity and mortality relapse disease free survival and overall survival
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 |
|---|---|---|---|
| 01-H-0010 | None | None | None |