Ignite Creation Date:
2024-05-05 @ 10:23 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005785
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2000-06-03
Brief Title:
Stem Cell Modified Bone Marrow Transplantation in HIV-Infected Patients With Blood Cancer
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Low Intensity Non-Myeloablative Preparative Conditioning Followed by Transplantation of Genetically Modified HLA-Matched Peripheral Blood Hematopoietic Precursor Cells PBPC for Hematologic Malignancies in HIV Positive Adults
Status:
COMPLETED
Status Verified Date:
2001-11
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 new stem cell transplant procedure to treat acute or chronic leukemia multiple myeloma myelodysplastic syndrome Hodgkins and non-Hodgkins lymphoma in HIV-infected patients
HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure This study uses a modified procedure transplanting stem cells instead of bone marrow designed to be less dangerous for such patients Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection The procedure in this study differs from standard bone marrow transplantation in three ways
Stem cells will be transplanted instead of bone marrow Stem cells which are produced by the bone marrow mature into the different blood components-white and red cells and platelets The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream The cells will then be collected from the donor by apheresis a procedure in which whole blood is drawn the stem cells separated and removed and the rest of the blood returned to the donor
The procedure will use lower doses of chemotherapy than the conventional method and will not use radiation therapy or
A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells rendering future cells that develop from resistance to the virus
Prospective patients will be tested for matching with an HIV-negative donor family member and will undergo a medical history physical examination and several tests eg breathing tests X-rays etc to determine eligibility for the study Study participants will then undergo apheresis to collect white blood cells called lymphocytes Stem cells will be collected from the donor Half the donated cells will have the HIV-resistant gene inserted the other half will have a control gene inserted Additional stem cells collected a second day will not be manipulated All the donor cells will be frozen until transplantation
Patients will be given drugs cyclophosphamide fludarabine and cyclosporin to prevent the donated cells from being rejected and to prevent them from damaging the patients organs The thawed stem cells will then be infused through a vein After 30 60 and 100 days bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin If less than 100 percent are of donor origin more lymphocytes will be transfused Patients will have physical examinations and blood tests once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years
HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure This study uses a modified procedure transplanting stem cells instead of bone marrow designed to be less dangerous for such patients Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection The procedure in this study differs from standard bone marrow transplantation in three ways
Stem cells will be transplanted instead of bone marrow Stem cells which are produced by the bone marrow mature into the different blood components-white and red cells and platelets The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream The cells will then be collected from the donor by apheresis a procedure in which whole blood is drawn the stem cells separated and removed and the rest of the blood returned to the donor
The procedure will use lower doses of chemotherapy than the conventional method and will not use radiation therapy or
A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells rendering future cells that develop from resistance to the virus
Prospective patients will be tested for matching with an HIV-negative donor family member and will undergo a medical history physical examination and several tests eg breathing tests X-rays etc to determine eligibility for the study Study participants will then undergo apheresis to collect white blood cells called lymphocytes Stem cells will be collected from the donor Half the donated cells will have the HIV-resistant gene inserted the other half will have a control gene inserted Additional stem cells collected a second day will not be manipulated All the donor cells will be frozen until transplantation
Patients will be given drugs cyclophosphamide fludarabine and cyclosporin to prevent the donated cells from being rejected and to prevent them from damaging the patients organs The thawed stem cells will then be infused through a vein After 30 60 and 100 days bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin If less than 100 percent are of donor origin more lymphocytes will be transfused Patients will have physical examinations and blood tests once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years
Detailed Description:
Adult patients with myelodysplasia leukemia and non-Hodgkins lymphoma can be cured by allogeneic bone marrow transplantation BMT This curative effect has until now been ascribed to the intense chemoradiotherapy used to condition the recipient for transplantation The assumption that the curative effect of allogeneic transplantation rests in the ability to deliver very high doses of chemoradiotherapy has led to the restriction of allogeneic transplantation to those recipient patients whose overall status would permit the use of such intense conditioning As a result HIV positivity has generally appeared as an exclusion criteria to allogeneic transplantation for hematologic malignancies Additionally early studies of allogeneic BMT in HIV patients suggested no benefit in controlling the progression to AIDS
Several in vitro studies have demonstrated the existence of donor derived CD4 and CD8 positive lymphocytes with specific reactivity to recipient leukemia providing a potent graft versus leukemia GVL effect and this GVL effect is area of intense interest both at the NIH and elsewhere In fact early attempts to decrease treatment related mortality in chronic myelogenous leukemia CML patients undergoing allogeneic BMT by T-cell depletion of the graft resulted in an unacceptably high rate of relapse suggesting that alloreactivity in the donor graft accounted for a significant portion of the cure rate in this disease This GVL effect is most dramatically demonstrated among relapsed allogeneic bone marrow transplant recipients transplanted for CML in whom a simple infusion of donor lymphocytes can induce a complete and durable remission
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated for engraftment efficacy and toxicity in a number of transplant centers Preliminary data including our own experience with 13 patients undergoing this type of procedure have shown a high rate of complete donor engraftment low toxicity and preservation of the GVL effect Two recent published studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant related complications and mortality
The decreased risk of transplant related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates and may allow successful application in patients infected with HIV In this study we will assess the safety and efficacy of nonmyeloablative transplantation in patients with HIV infection Moreover the introduction of an HIV resistance vector into a portion of the allogeneic graft provides a unique opportunity to test the in vivo efficacy of introducing resistance to HIV through the self renewing stem cell
The end points of this study are engraftment degree of donor-host chimerism incidence of acute and chronic GVHD transplant related morbidity and mortality disease free survival as well as overall survival and overall level and persistence of progeny of gene modified cells
Several in vitro studies have demonstrated the existence of donor derived CD4 and CD8 positive lymphocytes with specific reactivity to recipient leukemia providing a potent graft versus leukemia GVL effect and this GVL effect is area of intense interest both at the NIH and elsewhere In fact early attempts to decrease treatment related mortality in chronic myelogenous leukemia CML patients undergoing allogeneic BMT by T-cell depletion of the graft resulted in an unacceptably high rate of relapse suggesting that alloreactivity in the donor graft accounted for a significant portion of the cure rate in this disease This GVL effect is most dramatically demonstrated among relapsed allogeneic bone marrow transplant recipients transplanted for CML in whom a simple infusion of donor lymphocytes can induce a complete and durable remission
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated for engraftment efficacy and toxicity in a number of transplant centers Preliminary data including our own experience with 13 patients undergoing this type of procedure have shown a high rate of complete donor engraftment low toxicity and preservation of the GVL effect Two recent published studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant related complications and mortality
The decreased risk of transplant related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates and may allow successful application in patients infected with HIV In this study we will assess the safety and efficacy of nonmyeloablative transplantation in patients with HIV infection Moreover the introduction of an HIV resistance vector into a portion of the allogeneic graft provides a unique opportunity to test the in vivo efficacy of introducing resistance to HIV through the self renewing stem cell
The end points of this study are engraftment degree of donor-host chimerism incidence of acute and chronic GVHD transplant related morbidity and mortality disease free survival as well as overall survival and overall level and persistence of progeny of gene modified cells
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 |
|---|---|---|---|
| 99-DK-0167 | None | None | None |