Preventing Stem Cell Transplant Complications With a Blood Separator Machine
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|ClinicalTrials.gov Identifier: NCT01866839|
Recruitment Status : Completed
First Posted : June 3, 2013
Results First Posted : May 26, 2020
Last Update Posted : July 21, 2020
- 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 recipient's own body. Researchers want to test a blood separator machine that may help remove more of the donor's 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.
- To see if a new blood separator machine can improve outcomes of stem cell transplants.
- 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.
- 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 donor's 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.
|Condition or disease||Intervention/treatment||Phase|
|MDS (Myelodysplastic Syndrome) Myeloproliferative Disorder Lymphoma, Non-Hodgkin ALL (Acute B-Lymphoblastic Leukemia) AML (Acute Myelogenous Leukemia||Device: Graft Manipulation (CD34+ Selection)||Phase 1 Phase 2|
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 CliniMACS[registered] 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 CliniMACS[registered] 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 10(6)/kg and the target CD3+ dose range will be 5 x 10(4)/kg to 1 x 10(6)/kg. 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 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 selected for CD34+ progenitors using the Miltenyi CliniMACS[registered] 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Peripheral Blood Stem Cell Allotransplantation For Hematological Malignancies Using Ex Vivo CD34 Selection - a Platform For Adoptive Cellular Therapies|
|Study Start Date :||May 29, 2013|
|Actual Primary Completion Date :||May 23, 2018|
|Actual Study Completion Date :||June 28, 2018|
Experimental: CD34+ cell positively selected graft stem cell recipient
Recipients received a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg total), fludarabine (125 mg/m2 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 CliniMACS® system. Older subjects will receive a lower dose of irradiation (800 or 600 cGy based on age) to reduce the regimen intensity.
Device: Graft Manipulation (CD34+ Selection)
- Overall Survival [ Time Frame: 200 days ]Determine the rate of overall survival at 200 day
- Disease Free Survival at 2 Years [ Time Frame: 2 years ]Disease Free Survival at 2 years
- Disease Progression [ Time Frame: 3 years ]Incidence of relapse / disease progression
- Incidence of Acute GVHD [ Time Frame: 100 days ]Participants who develop acute GVHD
- Incidence of Chronic GVHD [ Time Frame: 3 years ]Participants who develop chronic GVHD
- Median Time to ANC>500/mm3 [ Time Frame: 3 years ]Time in days
- Median Time to Platelets>20K/mm3 [ Time Frame: 3 years ]Time in days
- Severity of Acute GVHD [ Time Frame: 100 days ]Grade I
- Severity of Acute GVHD [ Time Frame: 100 days ]Grade II
- Severity of Acute GVHD [ Time Frame: 100 days ]Grade III
- Severity of Acute GVHD [ Time Frame: 100 days ]Grade IV
- Severity of Chronic GVHD [ Time Frame: 3 years ]Extensive
- Severity of Chronic GVHD [ Time Frame: 3 years ]Limited
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01866839
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Sawa Ito, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|