Ignite Creation Date:
2024-05-06 @ 12:11 AM
Last Modification Date:
2024-10-26 @ 10:46 AM
Study NCT ID:
NCT01517035
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2012-01-24
Brief Title:
Improving Blood Stem Cell Collection and Transplant Procedures
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using Ex Vivo CD3 CD19 Depletion and CD34 Selection
Status:
COMPLETED
Status Verified Date:
2017-03-29
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:
Background
- People who have some kinds of cancer can benefit from donated bone marrow stem cells These stem cells help produce healthy bone marrow and slow or stop the spread of abnormal cells However stem cells transplants do not always work Also they may have serious side effects that can cause illness or death The Bone Marrow Stem Cell Transplant Program is studying methods to make stem cell transplant procedures safer and more effective
Objectives
- To test a new procedure that may improve the success and decrease the side effects of stem cell transplants
Eligibility
Individuals 10 to 75 years of age who have a life-threatening illness that may require a stem cell transplant
Healthy siblings who are able to provide stem cells for transplant
Design
Participants will be screened with a medical history physical exam and blood and urine tests
Donor procedures
Stem cell donors will start by having apheresis to donate white blood cells
Donors will receive filgrastim shots for 5 days to help move stem cells into the blood for collection
Donors will have another round of apheresis to donate the stem cells for transplant
Recipient procedures
Before the transplant recipients will have radiation twice a day for 3 days and chemotherapy for 7 days
After the radiation and chemotherapy recipients will receive the stem cells provided by the donor
After the transplant recipients will receive the white blood cells provided by the donor
Recipients will be monitored closely for 4 months to study the success of the transplant They will have more followup visits at least yearly thereafter
Recipients will have a research apheresis prior to transplant and at 3 months
- People who have some kinds of cancer can benefit from donated bone marrow stem cells These stem cells help produce healthy bone marrow and slow or stop the spread of abnormal cells However stem cells transplants do not always work Also they may have serious side effects that can cause illness or death The Bone Marrow Stem Cell Transplant Program is studying methods to make stem cell transplant procedures safer and more effective
Objectives
- To test a new procedure that may improve the success and decrease the side effects of stem cell transplants
Eligibility
Individuals 10 to 75 years of age who have a life-threatening illness that may require a stem cell transplant
Healthy siblings who are able to provide stem cells for transplant
Design
Participants will be screened with a medical history physical exam and blood and urine tests
Donor procedures
Stem cell donors will start by having apheresis to donate white blood cells
Donors will receive filgrastim shots for 5 days to help move stem cells into the blood for collection
Donors will have another round of apheresis to donate the stem cells for transplant
Recipient procedures
Before the transplant recipients will have radiation twice a day for 3 days and chemotherapy for 7 days
After the radiation and chemotherapy recipients will receive the stem cells provided by the donor
After the transplant recipients will receive the white blood cells provided by the donor
Recipients will be monitored closely for 4 months to study the success of the transplant They will have more followup visits at least yearly thereafter
Recipients will have a research apheresis prior to transplant and at 3 months
Detailed Description:
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on transplant techniques designed to decrease graft versus host disease GVHD increase the graft-versus-leukemia GVL effect and reduce the risk of post-transplant graft rejection
Through incremental transplant clinical trials we have shown that by controlling the stem cell CD34 cell and T lymphocyte CD3 cell dose severe GVHD can be reduced whilst beneficial GVL effects can be preserved We found that T cell depleted transplants using the NexellBaxter Isolex 300i system and subsequently the Miltenyi CD34 CliniMACs system to obtain high CD34 doses depleted of lymphocytes were safe to administer and associated with less severe acute GVHD and promising response rates and overall survival Our previous trials have helped us to create the transplant environment significant lymphodepletion and minimal post transplant immunosuppression that make for an ideal platform for adoptive cellular immunotherapy
This protocol is designed to evaluate the safety and efficacy of an improved ex vivo graft manipulation procedure using the Miltenyi CliniMACs CD 34 3 and 19 selection system in HLA-matched sibling allogeneic peripheral blood stem cell transplant The manipulation of the graft is the primary research intervention and all other aspects of clinical management on this protocol are the standard of care The target CD34 dose range will be 3 times 106kg to 10 times 106kg and the target CD3 dose range will be 5 x 104kg to 1 times 106kg The technique will preserve greater numbers of NK cells Once we demonstrate adequacy of engraftment in the first ten recipients we plan an amendment to permit further use of this protocol to serve as a platform for several planned adoptive cellular therapy initiatives
The protocol will accrue up to 44 subjects aged 10-75 with a hematological malignancy and their HLA-matched sibling donors in whom allogeneic stem cell transplantation from an HLA-matched sibling would be routinely indicated Diagnostic categories will include acute and chronic leukemia myelodysplastic syndromes lymphomas multiple myeloma and myeloproliferative syndromes
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide 120 mgkg total fludarabine 125 mgm2 total and total body irradiation 1200 cGy with lung shielding to 600 cGy followed by an infusion of a stem cell product prepared using the Miltenyi CliniMACS system for CD34 3 19 selection Older subjects will receive a lower dose of irradiation 600 cGy without lung shielding to reduce the regimen intensity
The overall objective is to assess the feasibility of using this system as a platform for cellular immunotherapy initiatives The primary study endpoint will be overall survival at day plus 200 Non-relapse mortality at day plus 200 will be monitored for safety Secondary endpoints will be standard transplant outcome variables such as non-hematologic toxicity incidence and severity of acute and chronic GVHD and relapse of disease
Through incremental transplant clinical trials we have shown that by controlling the stem cell CD34 cell and T lymphocyte CD3 cell dose severe GVHD can be reduced whilst beneficial GVL effects can be preserved We found that T cell depleted transplants using the NexellBaxter Isolex 300i system and subsequently the Miltenyi CD34 CliniMACs system to obtain high CD34 doses depleted of lymphocytes were safe to administer and associated with less severe acute GVHD and promising response rates and overall survival Our previous trials have helped us to create the transplant environment significant lymphodepletion and minimal post transplant immunosuppression that make for an ideal platform for adoptive cellular immunotherapy
This protocol is designed to evaluate the safety and efficacy of an improved ex vivo graft manipulation procedure using the Miltenyi CliniMACs CD 34 3 and 19 selection system in HLA-matched sibling allogeneic peripheral blood stem cell transplant The manipulation of the graft is the primary research intervention and all other aspects of clinical management on this protocol are the standard of care The target CD34 dose range will be 3 times 106kg to 10 times 106kg and the target CD3 dose range will be 5 x 104kg to 1 times 106kg The technique will preserve greater numbers of NK cells Once we demonstrate adequacy of engraftment in the first ten recipients we plan an amendment to permit further use of this protocol to serve as a platform for several planned adoptive cellular therapy initiatives
The protocol will accrue up to 44 subjects aged 10-75 with a hematological malignancy and their HLA-matched sibling donors in whom allogeneic stem cell transplantation from an HLA-matched sibling would be routinely indicated Diagnostic categories will include acute and chronic leukemia myelodysplastic syndromes lymphomas multiple myeloma and myeloproliferative syndromes
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide 120 mgkg total fludarabine 125 mgm2 total and total body irradiation 1200 cGy with lung shielding to 600 cGy followed by an infusion of a stem cell product prepared using the Miltenyi CliniMACS system for CD34 3 19 selection Older subjects will receive a lower dose of irradiation 600 cGy without lung shielding to reduce the regimen intensity
The overall objective is to assess the feasibility of using this system as a platform for cellular immunotherapy initiatives The primary study endpoint will be overall survival at day plus 200 Non-relapse mortality at day plus 200 will be monitored for safety Secondary endpoints will be standard transplant outcome variables such as non-hematologic toxicity incidence and severity of acute and chronic GVHD and relapse of disease
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 |
|---|---|---|---|
| 12-H-0028 | None | None | None |