Ignite Creation Date:
2024-05-06 @ 1:39 AM
Last Modification Date:
2024-10-26 @ 11:07 AM
Study NCT ID:
NCT01866839
Status:
COMPLETED
Last Update Posted:
2020-07-21
First Post:
2013-05-29
Brief Title:
Preventing Stem Cell Transplant Complications With a Blood Separator Machine
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 CD34 Selection - a Platform For Adoptive Cellular Therapies
Status:
COMPLETED
Status Verified Date:
2018-06-28
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
- Researchers are working to make stem cell transplant procedures safer and more effective One complication of transplants is graft-versus-host disease GVHD This complication happens when certain white blood cells from the donor attack the recipients own body Researchers want to test a blood separator machine that may help remove more of the donors white blood cells before transplant They will study donors and recipients during stem cell transplant to see how well this process can prevent GVHD and other complications
Objectives
- To see if a new blood separator machine can improve outcomes of stem cell transplants
Eligibility
Individuals between 10 and 75 years of age who are having a stem cell transplant for leukemia or other blood-related cancers
Donors for the stem cell transplant
Design
Recipients and donors will be screened with a physical exam and medical history
Donors will have two blood collection procedures The first will collect only white blood cells and return the rest of the blood After the first collection participants will have filgrastim injections to help their stem cells enter their blood Then they will have a second blood collection for the stem cells
Recipients will have radiation and chemotherapy to prepare for the stem cell transplant They will then have the stem cell transplant with the donor cells that have been treated with the blood separator machine
Recipients will be monitored closely after the procedure They may receive some of their donors white blood cells if needed to fight serious infections
Recipients will have the regular standard of care after their transplant Blood samples will be taken and any side effects will be monitored and treated
- Researchers are working to make stem cell transplant procedures safer and more effective One complication of transplants is graft-versus-host disease GVHD This complication happens when certain white blood cells from the donor attack the recipients own body Researchers want to test a blood separator machine that may help remove more of the donors white blood cells before transplant They will study donors and recipients during stem cell transplant to see how well this process can prevent GVHD and other complications
Objectives
- To see if a new blood separator machine can improve outcomes of stem cell transplants
Eligibility
Individuals between 10 and 75 years of age who are having a stem cell transplant for leukemia or other blood-related cancers
Donors for the stem cell transplant
Design
Recipients and donors will be screened with a physical exam and medical history
Donors will have two blood collection procedures The first will collect only white blood cells and return the rest of the blood After the first collection participants will have filgrastim injections to help their stem cells enter their blood Then they will have a second blood collection for the stem cells
Recipients will have radiation and chemotherapy to prepare for the stem cell transplant They will then have the stem cell transplant with the donor cells that have been treated with the blood separator machine
Recipients will be monitored closely after the procedure They may receive some of their donors white blood cells if needed to fight serious infections
Recipients will have the regular standard of care after their transplant Blood samples will be taken and any side effects will be monitored and treated
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 CliniMACSregistered CD34 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 Adoptive cell transfer is the passive transfer of immune cells into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host
This protocol is designed to evaluate the safety and efficacy of the Miltenyi CliniMACSregistered CD 34 selection system in HLA-matched sibling allogeneic peripheral blood stem cell transplant The manipulation of the graft is the primary research intervention subject to IDE 15632 and all other aspects of clinical management on this protocol are standard care The target CD34 dose range will be 3 x 106kg and the target CD3 dose range will be 5 x 104kg to 1 x 106kg Once we demonstrate adequacy of this platform for engraftment and absence of significant GVHD in ten consecutive recipients we will seek IRB permission to proceed with planned adoptive cellular therapies
The protocol will accrue up to 96 transplant recipients aged 10-80 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 selected for CD34 progenitors using the Miltenyi CliniMACSregistered system Older subjects will receive a lower dose of irradiation 800 or 600 cGy based on age 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 200 Stopping criteria for safety will monitor non-relapse mortality at day 200 and late disease free survival at 2 years 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 CliniMACSregistered CD34 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 Adoptive cell transfer is the passive transfer of immune cells into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host
This protocol is designed to evaluate the safety and efficacy of the Miltenyi CliniMACSregistered CD 34 selection system in HLA-matched sibling allogeneic peripheral blood stem cell transplant The manipulation of the graft is the primary research intervention subject to IDE 15632 and all other aspects of clinical management on this protocol are standard care The target CD34 dose range will be 3 x 106kg and the target CD3 dose range will be 5 x 104kg to 1 x 106kg Once we demonstrate adequacy of this platform for engraftment and absence of significant GVHD in ten consecutive recipients we will seek IRB permission to proceed with planned adoptive cellular therapies
The protocol will accrue up to 96 transplant recipients aged 10-80 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 selected for CD34 progenitors using the Miltenyi CliniMACSregistered system Older subjects will receive a lower dose of irradiation 800 or 600 cGy based on age 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 200 Stopping criteria for safety will monitor non-relapse mortality at day 200 and late disease free survival at 2 years 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?:
False
Is a FDA Regulated Device?:
True
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 |
|---|---|---|---|
| 13-H-0144 | None | None | None |