Stem Cell Transplant for Bone Marrow Failure Syndrome
(ExpMACs Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Children's Hospital of Philadelphia
Disqualifiers: Infections, HLA matched sibling, pregnancy
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this protocol is to expand access for patients who lack a fully HLA (Human leukocyte antigen) matched sibling donor and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-threatening disease for which HSCT is indicated. These patients are not eligible for other Children's Hospital of Philadelphia IRB approved protocols that utilize CliniMACs technology for T depletion.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment 'Stem Cell Transplant for Bone Marrow Failure Syndrome' involving CD3+/CD19+ depletion?
Research shows that depleting specific immune cells (TCRαβ+ T cells and CD19+ B cells) from stem cell transplants can help reduce complications like graft-versus-host disease (a condition where the donor cells attack the recipient's body) and improve outcomes in similar treatments for conditions like leukemia and severe combined immunodeficiency.
12345Is the stem cell transplant with CD3+/CD19+ depletion generally safe for humans?
Research shows that using the CliniMACS system for stem cell transplants with CD3+/CD19+ depletion is generally safe. It effectively removes certain immune cells to reduce complications like graft-versus-host disease (a condition where transplanted cells attack the recipient's body) without harming the stem cells' function.
12356How is the stem cell transplant treatment with CD3+/CD19+ depletion different from other treatments for bone marrow failure syndrome?
This treatment is unique because it involves selectively removing specific immune cells (T and B cells) from the donor stem cell graft to reduce the risk of complications like graft-versus-host disease, while preserving other beneficial cells like natural killer cells, which can improve patient outcomes.
12357Eligibility Criteria
This trial is for patients without a fully matched sibling donor who need a stem cell transplant due to serious conditions like leukemia, metabolic diseases correctable by HSCT, bone marrow failure, or immune system problems. They must meet specific health criteria and not be pregnant or have uncontrolled infections.Inclusion Criteria
My organ functions meet the required levels, and I don't have an untreated infection.
You don't have a fully matched sibling for a specific type of stem cell transplant, and you don't meet the requirements for other treatment options at the hospital.
I am capable of becoming pregnant and have a negative pregnancy test.
+3 more
Exclusion Criteria
My donor cannot give stem cells through their bloodstream.
I am currently pregnant.
I do not have any ongoing serious infections.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants undergo allogeneic hematopoietic stem cell transplant (HSCT) with CD3+/CD19+ depleted stem cells
4-6 weeks
Follow-up
Participants are monitored for safety and effectiveness after the transplant, focusing on complications such as graft vs. host disease (GVHD)
12 weeks
Participant Groups
The trial provides access to a special stem cell transplant using CliniMACs technology to deplete certain cells (CD3+/CD19+) from the donated material. It's aimed at those who can't participate in other trials but need this potentially life-saving procedure.
1Treatment groups
Experimental Treatment
Group I: Expanded access to CliniMACs device for T cell depletionExperimental Treatment1 Intervention
access for patients who lack a fully HLA matched sibling, and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-open protocols that utilize CliniMACs technology for T depletion. Subjects will undergo transplant of stem cells with CD3+/CD19+ depletion.
Transplant of stem cells with CD3+/CD19+ depletion (CliniMACs) is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as CD3+/CD19+ depleted PBSC for:
- Hematologic malignancies
- Hemoglobinopathies
- Primary immunodeficiencies
🇺🇸 Approved in United States as CD3+/CD19+ depleted PBSC for:
- Hematologic malignancies
- Hemoglobinopathies
- Primary immunodeficiencies
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's Hospital of PhiladelphiaPhiladelphia, PA
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Who Is Running the Clinical Trial?
Children's Hospital of PhiladelphiaLead Sponsor
References
[An effective method for T-cell and B-cell simultaneous depletion in vitro from mobilized peripheral blood stem/progenitor cell graft for haploidentical transplantation]. [2017]Depletion of T and B cells from the graft is prerequisite for haploidentical transplantation to decrease the risk of GVHD and EBV-associated lymphoproliferative disease. This study was aimed to investigate the performance of T-cell and B-cell simultaneous depletion from mobilized peripheral blood stem cells (PBSCs) for the first time in China, using anti-CD3 and anti-CD19 antibodies conjugated to magnetic microbeads by the CliniMACS device. The depletion efficiency of T-cell and B-cells was analyzed by flow cytometry; the function of the stem cells after depletion was evaluated using colony assays. The results indicated that the mononuclear cell count prior to T- and B-cell depletion was 4.88 x 10(10). After depletion, the percentage of T cells was 0.02% with a log (10) depletion of 4.4. The percentage of B cells was less than 0.01% with a log (10) depletion of at least 3.3. The product contained not only CD34(+) stem cells, but also NK cells, monocytes and granulocytes. After T- and B-cell depletion the purity of CD34(+) cells was 0.98%, the number of CD34 cells was 1.84 x 10(8) and their recovery rate was 69.7%. The number of NK cells was 2.54 x 10(9) and the recovery rate of NK cells was 71.7%. In vitro colony assays showed no negative impact on function of the hematopoietic stem cells. In conclusion, the CliniMACS system can be used to efficiently deplete T and B cells from PBSCs simultaneously, without adverse effect on biological function of hematopoietic stem cells. This study provides technical platform for haploidentical hematopoietic stem cell transplantation.
Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions. [2018]Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for severe combined immunodeficiency (SCID); although, there is a high incidence of severe infections and an increased risk of graft-versus host-disease (GvHD) with HSCT. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. Haploidentical HSCT protocols utilizing extensively ex vivo T-cell depleted grafts (CliniMACs system) have proven efficient in preventing GvHD, but cause a delay in early T-cell recovery that increases the risk of viral infections. Here, we present a novel approach for treating SCID that combines selective depletion of GvHD-inducing alpha/beta (α/β) T-cells from the haploidentical HSCT graft with a subsequent donor lymphocyte infusion (DLI) enriched for CD45RO+ memory T-cells.
Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy: Results of 10 Graft-Processing Procedures from Haploidentical Donors. [2022]Depletion of TCRαβ+ T cells and B cells with the CliniMACS Plus® has been used for haploidentical hematopoietic stem cell transplantation for a decade. The depletion procedure is time and labour demanding and with variable reported efficiencies. Recently, an automated procedure was launched for the CliniMACS Prodigy® (Miltenyi Biotec) but reported data are scarce. Here, we report the results of the first ten TCRαβ+ and B cell depletion procedures for clinical use performed at our centre.
TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. [2022]We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated (n=20) and haploidentical donors (n=13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 10(6)/kg of CD34+ and 20 × 10(3)/kg of αβ-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40-204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2-3 was 39 (26-60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18-50)%. Transplant-related mortality is 10(4-26)%. Event-free survival (EFS) is 60(43-76)% and overall survival (OS) is 67(50-84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48-84)% and OS-72(53-90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML.
Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product. [2023]In vitro or in vivo depletion of alloreactive T cells can facilitate haplo-identical hematopoietic stem cell transplantation (HSCT). Very satisfactory transplant outcomes were thus reported for TCRαβ/CD19-depleted hematopoietic stem/progenitor cell (HSPC) grafts. The current semi-automatic manufacturing process on the CliniMACS Plus, although robust, still requires a significant amount of manual labor to be completed. Towards advancing and further facilitating large scale cell processing, a new TCRαβ/CD19 depletion module combined with the previously described CD45RA depletion module (to serve as allo-reactivity attenuated donor lymphocyte infusion) was established on the CliniMACS Prodigy.
A CD34+ Cell Enrichment Protocol of Hematopoietic Stem Cells in a Well-Established Quality Management System. [2020]Allogeneic stem cell transplantation applications have improved tremendously over the past quarter of a century. The use of new immunosuppressive protocols and elimination of T cells by CD34+ cell enrichment or T cell depletion on apheresis products increases the chance of using partially matched or haploidentical grafts. This is without increasing the risk of graft-versus-host disease, which is observed as a major complication of hematopoietic stem cell transplantation. The aim of this protocol is to evaluate the results obtained from 6 different process cycles performed on 6 different days. We used the CliniMACS Plus system located in our Cell and Tissue Manufacturing Center Quality Control Unit which is already calibrated as a class D room and includes a class A microbiological safety cabinet inside. The average purity of the end products was 95.66%, excluding only one end product which was 70%; this was higher than the values in current studies in the field. Superior to the reported studies, the CD3 quantity in each end product was below the dedicated thresholds. BactecTM FX40 blood culture system test results were detected as negative for each end product. Endotoxin testing suggested the absence of endotoxin within the products. The consistent outcomes obtained from these 6 different process cycles confirmed that the CliniMACS® Plus process cycles performed in accordance with our well-defined quality management system procedure is sufficient for the routine application of high-quality and safe CD34+ enrichment processes within our clean room area.
CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust. [2021]Aggressive T-cell depletion, in vitro or in vivo, is a prerequisite for survival of haplo-identical stem cell transplantation. The classical T-cell-depleted transplant, immunomagnetically enriched CD34+ cells, is very safe with respect to graft-versus-host reactivity, but associated with very high transplant-related and relapse mortality with an overall probability of survival of only 20%. Protocols for T- and B-cell depletion were therefore developed, reasoning that transplantation of the majority of Natural Killer (NK) cells and the substantial dose of residual T-cells might improve survival, which was, in principle, confirmed. Anecdotal reports of frequent failure to achieve adequate T-cell depletion prompted review of the aggregate data for transplant quality at our center. The first observation is the relative paucity of combined CD3/CD19 depletion processes as PTCy protocols have made inroads, 13 depletions in 8 years. Median T- and B-cell log-depletion were -3.89 and -1.92, respectively; instead of, CD34+ cell recovery was generally high (median 92%), as was NK-cell recovery (median 52%). However, the process failed to yield satisfactory T- and B-cell depletion in two out of 13 preparations, of which one product could be rescued by a second round of depletion, at the expense of CD34+ cell recovery. In our hands, the process is thus insufficiently robust for routine clinical use. Assuming similar observations in other centers, this may explain implementation of alternative protocols, such as TCRαβ/CD19 depletion or transplantation of unmanipulated grafts with subsequent in vivo depletion.