CliniMACS® T-Cell Depletion for Stem Cell Transplant Patients
Recruiting in Palo Alto (17 mi)
Overseen byChristopher C Dvorak, MD
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Christopher Dvorak
Disqualifiers: Pregnant, Life expectancy <1 month, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Patients in need of an allogeneic hematopoietic cell transplant (HCT) are at risk of developing graft-versus-host-disease (GVHD). In certain clinical situations, the optimal approach to minimize the risk of GVHD is to perform ex vivo alpha-beta T-cell depletion of the donor cells. However, the CliniMACS® Device is FDA-approved only for a narrow indication. All other uses of ex vivo processed cells must be done under a feasibility study protocol.
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 CliniMACS® T-Cell Depletion treatment for stem cell transplant patients?
Research shows that the CliniMACS system effectively purifies and recovers CD34+ cells (important stem cells) while efficiently removing T cells, which can help reduce complications in stem cell transplants. This method has been used successfully in both children and adults with severe blood disorders and autoimmune diseases, showing higher purity and recovery rates compared to other methods.
12345Is CliniMACS® T-Cell Depletion safe for humans?
The CliniMACS® system, used for T-cell depletion in stem cell transplants, has shown consistent safety in studies, with no endotoxins (harmful substances) detected and negative results for bacterial contamination. It has been used successfully in both children and adults for various conditions, indicating a generally safe profile.
12356How is the CliniMACS® treatment different from other treatments for stem cell transplant patients?
The CliniMACS® treatment is unique because it uses a magnetic separation technique to efficiently deplete T cells from stem cell grafts, resulting in higher purity and recovery of CD34+ cells compared to other methods. This approach helps reduce the risk of complications like graft-versus-host disease in stem cell transplants.
12357Eligibility Criteria
This trial is for males and females aged 0-30 needing a stem cell transplant due to certain diseases, with donors available who can give bone marrow or blood stem cells. It's not for those with identical related donors (unless they have Fanconi Anemia), life expectancy under one month, mouse protein or iron dextran allergies, pregnant/breastfeeding individuals, or if birth control isn't used.Inclusion Criteria
Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study
I have a healthy donor ready to give bone marrow or stem cells.
My condition requires a stem cell transplant.
+1 more
Exclusion Criteria
Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
I have a healthy, willing, and HLA-matched relative to donate (unless I have Fanconi Anemia).
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive alpha-beta T-cell depleted stem cell transplants using the CliniMACS system
Up to 30 days
Multiple visits for infusion and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including engraftment and GVHD evaluations
12 months
Regular visits for monitoring and assessments
Long-term follow-up
Participants are monitored for long-term outcomes such as transplant-related mortality and chronic GVHD
12 months
Participant Groups
The study tests the CliniMACS® Device's ability to remove specific T-cells from donor cells before transplant to prevent graft-versus-host disease. This process is being evaluated as it's currently only FDA-approved for limited use and needs further investigation in other settings.
1Treatment groups
Experimental Treatment
Group I: Patients receiving allogeneic hematopoietic cell transplantExperimental Treatment1 Intervention
The test product is a stem cell product which has been alpha-beta T- cell depleted using the CliniMACS system. Alpha-beta T-cell depleted cells are given intravenously over a period of time as dictated by the final volume of the infused product (5 ml/kg/hour).
The target dose of CD34+ cells is ≥20x10\^6/kg, but a minimum of
≥2.5x10\^6/kg is required. The target dose of T-cell receptor (TCR) alpha-beta CD3+ cells is ≤1x10\^5/kg.
CliniMACS® is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as CliniMACS CD34 Reagent System for:
- Prevention of graft-versus-host disease (GVHD) in patients with acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic cell transplant from a matched related donor
🇪🇺 Approved in European Union as CliniMACS System for:
- Available as CE-marked medical devices for various cell separation and processing applications, but specific indications are not detailed beyond general use for hematopoietic cell processing
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, San FranciscoSan Francisco, CA
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Who Is Running the Clinical Trial?
Christopher DvorakLead Sponsor
References
Comparison of two different methods for CD34+ selection and T cell depletion in peripheral blood stem cell grafts--our experiences with CellPro, E rosetting and CliniMACS technique. [2006]The aim of this study was to establish a suitable method for in vitro T cell depletion in peripheral blood stem cell grafts for mismatched/haploidentical transplantation in children and adults with severe hematological disorders and for autologous transplantation in patients with autoimmune diseases refractory to conventional immunosuppressive treatment. Two different selection techniques have been used: CD34+ selection using immunoaffinity columns (CellPro Ceprate) followed by T cell depletion by E-rosetting or CD34+ selection using submicroscopic paramagnetic beads (CliniMACS device) with T cell depletion in a one step procedure. The mean purity and recovery of CD34+ cells and efficiency of T cell removal in the final product were compared. From March 1995 to December 1998 we prepared twelve allografts using Cell Pro system for eight children with high-risk hematological malignancies and six autografts for six patients with severe autoimmune diseases. From January 1999 to October 2000 we prepared fifteen allografts using CliniMACS system for ten children with high-risk hematological diseases and inborn metabolic disorders or primary immunodeficiences, five allografts for three adult patients with high-risk hematological malignancies and two autografts for two patients with autoimmune diseases. In allogeneic transplantation the median purity of CD34+ cells in the final products after CellPro and E-rosetting was 85.6% (55.3%-95.7%); median recovery was 24.8% (17%-35%), median transplanted doses of T cells per kilogram of body weight were 0.66x10(4) (0-2.8); in autologous transplantation the median purity of CD34+ was 92.6% (55.6%-96%), median recovery was 28% (22%-46.2%), median transplanted doses of T cells per kilogram of body weight were 0.39x10(4) (0.0-3.6). After CliniMACS technique the median purity of CD34+ cells was 94.87% (69.15%-99%),medianrecoverywas 58% (30%-79.6%), median transplanted doses of T cells per kg of body weight were 0.254x10(4) (0-14.15); in autologous transplantation the median purity of CD34+ was 94% (94%-94%, median recovery was 97.4% (95%-99.8%), median transplanted doses of T cells per kilogram of body weight were 0.87x10(4) (0.49-1.24). We consider both methods of CD34+ selection and T cell depletion suitable for peripheral blood stem cell processing before mismatched hemopoietic stem cell transplantation in patients without identical donor or before autologous transplantation for severe autoimmune diseases. However, magnetic separation using CliniMACS system results in higher levels of purity and recovery with efficient T cell depletion.
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.
Automated CD34+ cell isolation of peripheral blood stem cell apheresis product. [2018]Immunomagnetic enrichment of CD34+ hematopoietic "stem" cells (HSCs) using paramagnetic nanobead coupled CD34 antibody and immunomagnetic extraction with the CliniMACS plus system is the standard approach to generating T-cell-depleted stem cell grafts. Their clinical beneficence in selected indications is established. Even though CD34+ selected grafts are typically given in the context of a severely immunosuppressive conditioning with anti-thymocyte globulin or similar, the degree of T-cell depletion appears to affect clinical outcomes and thus in addition to CD34 cell recovery, the degree of T-cell depletion critically describes process quality. An automatic immunomagnetic cell processing system, CliniMACS Prodigy, including a protocol for fully automatic CD34+ cell selection from apheresis products, was recently developed. We performed a formal process validation to support submission of the protocol for CE release, a prerequisite for clinical use of Prodigy CD34+ products.
Haploidentical bone marrow transplantation in Mexico. [2012]Haploidentical hematopoietic cell transplantation using CD34(+) cells depleted of T lymphocytes by the CliniMACS is a treatment for hematological malignancy. We report on four Mexican children, three with acute lymphocytic leukemia and one with chronic myelocytic leukemia, who was transplanted with 12 × 10(6) CD34(+) stem cells/kg body weight (98% of purity) with a follow-up of 9½ years. The engraftment was successful in three of the four children. All showed cytomegalovirus reactivation, and one died because of graft rejection and infectious complication. The risk of infections was a major problem.
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.
Improved immunomagnetic enrichment of CD34(+) cells from umbilical cord blood using the CliniMACS cell separation system. [2021]CD34(+) enrichment from cord blood units (CBU) is used increasingly in clinical applications involving ex vivo expansion. The CliniMACS instrument from Miltenyi Biotec is a current good manufacturing practice (cGMP) immunomagnetic selection system primarily designed for processing larger numbers of cells: a standard tubing set (TS) can process a maximum of 60 billion cells, while the larger capacity tubing set (LS) will handle 120 billion cells. In comparison, most CBU contain only 1-2 billion cells, raising a question regarding the optimal tubing set for CBU CD34(+) enrichment. We compared CD34(+) cell recovery and overall viability after CliniMACS processing of fresh CBU with either TS or LS.
[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.