CliniMACS® for Blood Cancers
(TB19DHCT Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Nationwide Children's Hospital
Disqualifiers: HIV, Uncontrolled infections, Pregnancy, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This is a study utilizing the Magnetic-activated cell sorting (CliniMACS®) Alpha-Beta T-cell (αβT)/Cluster of Differentiation 19 (CD19), also called B lymphocyte antigen CD19 depletion device for Children and Young Adults with Hematologic Malignancies undergoing alternative Donor Allogeneic Hematopoietic Cell Transplantation (HSCT). Patients will receive an allogenic HSCT from a matched unrelated donor (MUD), mismatch unrelated donor (MMUD) or a mismatched related (haploidentical) donor. Patients will receive a granulocyte-colony stimulating factor (G-CSF) ± Plerixafor donor mobilized peripheral stem cell donor transplant following CliniMACS® αβT cell/CD19+B cell depletion. Cluster of Differentiation 34 (CD34) and αβT cell content of the graft is determined based on the transplant indication.
Do I need to stop my current medications for the trial?
The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the CliniMACS® treatment for blood cancers?
How is the CliniMACS treatment different from other treatments for blood cancers?
The CliniMACS treatment is unique because it uses a magnetic-activated cell separation system to enrich CD34+ stem cells, which helps reduce tumor cell contamination in stem cell transplants. This method is particularly beneficial for patients undergoing autologous (self-donated) or allogeneic (donor) stem cell transplants, as it provides a high-purity graft with low T-cell content, potentially reducing the risk of relapse.26789
Eligibility Criteria
This trial is for children and young adults up to 30 years old with blood cancers who need a bone marrow transplant but don't have a matched sibling donor. They should be in good health otherwise, able to tolerate the transplant process, and have an acceptable performance status score.Inclusion Criteria
I am 30 years old or younger.
I have a detailed HLA test result available.
I need a stem cell transplant for my blood cancer and don't have a matching sibling donor.
See 4 more
Exclusion Criteria
Patient reports a history of allergic reactions to murine protein
I do not have a suitable donor available for my treatment.
I am receiving a transplant from umbilical cord blood or a sibling match.
See 2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive an allogeneic HSCT from a matched unrelated donor (MUD), mismatch unrelated donor (MMUD) or a mismatched related (haploidentical) donor following CliniMACS® αβT cell/CD19+B cell depletion
100 days
Follow-up
Participants are monitored for safety and effectiveness after treatment, including overall survival and incidence of graft failure and GVHD
1 year
Treatment Details
Interventions
- CliniMACS® (Cell Depletion)
Trial OverviewThe study tests CliniMACS® device's ability to deplete specific immune cells (αβT/CD19+ B cells) from stem cell grafts before transplantation. It aims to see if this can help patients accept cells from partially matched or unrelated donors without complications.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: HSCT using TCR αβ/CD19+ depleted graftsExperimental Treatment1 Intervention
Allogeneic HSCT using the TCR αβ/CD19+ depleted platform and grafts from alternative donors (MUD, MMUD and haploidentical)
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:
Nationwide Children's HospitalColumbus, OH
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Who Is Running the Clinical Trial?
Nationwide Children's HospitalLead Sponsor
References
Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. [2021]We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.
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.
Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. [2020]Optimization of Hematology Patient's treatment: It is possible to obtain a 100% CD34+ recovery after CD34+ selection using 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.
Robust Selections of Various Hematopoietic Cell Fractions on the CliniMACS Plus Instrument. [2021]Cell separation technologies play a vital role in the graft engineering of hematopoietic cellular fractions, particularly with the rapid expansion of the field of cellular therapeutics. The CliniMACS Plus Instrument (Miltenyi Biotec) utilizes immunomagnetic techniques to isolate hematopoietic progenitor cells (HPCs), T cells, NK cells, and monocytes. These products are ultimately used for HPC transplantation and for the manufacture of adoptive immunotherapies. We evaluated the viable cell recovery and cell purity of selections and depletions performed on the CliniMACS Plus over a 10-year period at our facility, specifically assessing for the isolation of CD34+, CD4+, CD3+/CD56+, CD4+/CD8+, and CD25+ cells. Additionally, patient- and instrument-related factors affecting these parameters were examined. Viable cell recovery ranged from 32.3 ± 10.2% to 65.4 ± 15.4%, and was the highest for CD34+ selections. Cell purity ranged from 86.3 ± 7.2% to 99.0 ± 1.1%, and was the highest for CD4+ selections. Undesired cell fractions demonstrated a range of 1.2 ± 0.45 to 5.1 ± 0.4 log reductions. Red cell depletions averaged 2.12 ± 0.68 logs, while platelets were reduced by an average of 4.01 ± 1.57 logs. Donor characteristics did not impact viable cell recovery or cell purity for CD34+ or CD4+ cell enrichments; however, these were affected by manufacturing variables, including tubing size, bead quantity, and whether preselection platelet washes were performed. Our data demonstrate the efficient recovery of hematopoietic cellular fractions on the CliniMACS Plus that may be optimized by adjusting manufacturing variables.
CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device. [2019]Several devices for selection of CD34+ peripheral blood stem cells (PBSC) have been used during the last years for reducing tumor cell contamination of the graft. The new CliniMACS system (magnetic-activated cell separation system by Miltenyi Biotech GmbH, Bergisch-Gladbach, Germany) was recently approved for clinical use in Europe. To evaluate its purging efficiency and engraftment data in the autologous transplant, PBSC from 28 adult patients with various malignant diseases (non-Hodgkin's lymphoma, n = 17; chronic lymphocytic leukemia, n = 5; multiple myeloma, n = 4; acute lymphocytic leukemia, n = 1; medulloblastoma, n = 1) were mobilized by chemotherapy and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg per day). Thirty leukapheresis products from 28 patients with a median of 4.4 x 10(8) nucleated cells/kg body weight (bw)(range 0.6-10.8 x 10(8)/kg bw) and a median of 7.1 x 10(6) CD34+ cells/kg bw (range 2.8 to 18.8 x 10(6)/kg bw) were selected using the Cobe spectra cell separator (Cobe BCT Inc., Lakewood, CO). After the CliniMACS procedure, the median yield of CD34+ selected cells was 4.5 x 10(6)/kg (range 2.2-11.1 X 10(6)/kg bw) with a median recovery of 69.5% (range 46.9-87.3%) and a median purity of 97.7% (range 89.4-99.8%). The procedure did not alter viability of selected cells, which was tested by propidium iodide staining. So far, purified PBSC were used for autologous transplantation in 15 out of 28 patients after total body irradiation and/or high-dose chemotherapy. Median time to reach an absolute neutrophil count > 500/microl was 12 days (range 10-18 days), platelet recovery >50,000/microl occurred at day + 16 (range 11-22). With a median follow-up time of 12 months (range 3-19), 5 patients died of relapse. We confirmed the feasibility and safety of the CliniMACS CD34+ cell enrichment procedure in adult patients with autologous PBSC transplantation.
Evaluation of 'out-of-specification' CliniMACS CD34-selection procedures of hematopoietic progenitor cell-apheresis products. [2019]Immunomagnetic selection of CD34(+) hematopoietic progenitor cells (HPC) using CliniMACS CD34 selection technology is widely used to provide high-purity HPC grafts. However, the number of nucleated cells and CD34+ cells recommended by the manufacturer for processing in a single procedure or with 1 vial of CD34 reagent is limited.
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.
Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience. [2008]Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies.