Ignite Creation Date:
2025-12-24 @ 10:06 PM
Ignite Modification Date:
2025-12-25 @ 7:43 PM
Study NCT ID:
NCT01517035
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2012-01-24
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Improving Blood Stem Cell Collection and Transplant Procedures
Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Organization:
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 Nexell/Baxter 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 10(6)/kg to 10 times 10(6)/kg and the target CD3+ dose range will be 5 x 10(4)/kg to 1 times 10(6)/kg. 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 mg/kg total), fludarabine (125 mg/m(2) 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 Nexell/Baxter 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 10(6)/kg to 10 times 10(6)/kg and the target CD3+ dose range will be 5 x 10(4)/kg to 1 times 10(6)/kg. 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 mg/kg total), fludarabine (125 mg/m(2) 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:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 12-H-0028 | None | None | View |