Trial Summary
What is the purpose of this trial?This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells combined with single unit umbilical cord blood transplant for treatment of high-risk hematologic disorders.
Do I need to stop my current medications for this trial?
The trial protocol does not specify whether you need to stop taking your current medications.
What data supports the idea that Haploidentical Transplant for Blood Disorders is an effective treatment?
The available research shows that Haploidentical Transplant for Blood Disorders, when combined with umbilical cord blood, can lead to successful outcomes. In one study, 83% of patients experienced successful engraftment, which means the transplanted cells started to grow and produce healthy blood cells. Additionally, the study reported a 54% overall survival rate at one year, indicating that more than half of the patients were still alive after a year. This suggests that the treatment can be effective for patients who do not have a fully matched donor. Compared to other methods, such as using two mismatched cord blood units, this approach provides a viable alternative with rapid recovery of blood cells and a lower risk of complications like graft-versus-host disease, where the new immune cells attack the patient's body.
12345What safety data is available for haploidentical transplants for blood disorders?
The safety data for haploidentical transplants, including those using CD34+ selected cells combined with umbilical cord blood, indicates that this approach can result in rapid engraftment with no increased rate of graft failure or graft-versus-host disease (GVHD). In a study of 26 patients, the incidence of grade 2-4 acute GVHD was 27% at day +100, and chronic GVHD was 4% at 1 year. Overall survival at 1 year was 54%. Recent advances have reduced historical issues of graft rejection and severe GVHD, making haploidentical stem cell transplantation a viable option for patients without a fully matched donor. However, post-transplant infectious complications and relapse remain challenges.
16789Is the treatment Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant a promising treatment for blood disorders?
Yes, this treatment is promising because it provides an alternative for patients who don't have a fully matched donor. It allows for nearly immediate donor availability and has shown improved outcomes over the past decade. This approach helps meet the need for stem cell transplants, especially for those with diverse backgrounds or urgent needs.
1011121314Eligibility Criteria
This trial is for adults aged 18-80 with high-risk blood disorders who lack an exact HLA-matched donor but have a partially matched (5/10 to 8/10) relative and a suitable umbilical cord blood unit. It's not open to those with a fully matched (6/6) related donor or who don't meet standard transplant guidelines.Inclusion Criteria
I have a cord blood match with at least 4/6 HLA compatibility and enough cells for my body weight.
I have a family donor who is a partial match for a stem cell transplant.
I understand the treatment I will be receiving.
+3 more
Exclusion Criteria
I have a family donor who is a perfect match for my transplant.
Any patient not meeting institutional standard guidelines for transplant eligibility
Participant Groups
The study tests the Miltenyi CliniMACS® CD34 Reagent System, aiming to improve how well patients accept stem cells from partly matched relatives combined with umbilical cord blood transplants in treating serious blood diseases.
1Treatment groups
Experimental Treatment
Group I: Miltenyi CliniMACS® CD34 Reagent SystemExperimental Treatment1 Intervention
The haploidentical donor will be mobilized by G-CSF and undergo one apheresis to collect CD34+ selected stem cell product after Miltenyi CliniMACS® CD34+ selection. The products will be cryopreserved until the time of transplantation.
Recipients will receive a standard conditioning regimen. After the conditioning regimen, the subjects will receive an allograft on day 0 containing donor CD34+ cells that have been positively selected and T-cell depleted following G-CSF mobilization combined with a single UCB unit. UCB unit will not be manipulated, and will be prepared and infused separately following standard of care procedure.
Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant is already approved in United States for the following indications:
🇺🇸 Approved in United States as CliniMACS CD34 Reagent System for:
- Processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA-identical, sibling donor to obtain a CD34+ cell-enriched population for hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional graft versus host disease (GVHD) prophylaxis in patients with acute myeloid leukemia (AML) in first morphologic complete remission.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of ColoradoAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
References
Cord blood transplants supported by unrelated donor CD34+ progenitor cells. [2021]Alternative donor transplantation with the haplo-cord platform allows the use of a lower-dose single umbilical cord blood unit (CBU) by co-infusion of third-party CD34+-selected cells from a haploidentical relative, which provides early transient engraftment while awaiting durable CBU engraftment. In our experience, ~15% of patients lack a suitable haploidentical donor. Here we report 26 patients who underwent haplo-cord transplant using CD34+-selected partially matched unrelated donor grafts. Twenty-four were conditioned with fludarabine/melphalan +/- low-dose TBI (n = 16). Twenty-five received ATG and all received posttransplant tacrolimus and mycophenolate mofetil. Median time to neutrophil and platelet recovery was 11 and 18 days. CBU engraftment, with CD33 and CD3 >5% cord chimerism in the myeloid/lymphoid compartment by day +60, occurred in 20 of 24 patients (83%). Incidence of grade 2-4 acute graft-versus-host disease (GVHD) was 27% at day +100, and chronic GVHD was 4% at 1 year. Overall survival at 1 year was 54%. For patients in need of an alternative transplant who lack a haploidentical donor, haplo-cord transplantation using CD34+-selected partially matched unrelated donor grafts results in rapid engraftment with no increased rate of cord graft failure or GVHD.
Double-chimaerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. [2019]The small number of progenitor cells is the major limitation to the use of umbilical cord blood (UCB) for the transplantation of adults. We tested the hypothesis that two units transplanted simultaneously could each contribute to haematopoietic reconstitution. A patient with advanced acute lymphocytic leukaemia received a mismatched, unrelated UCB transplant using units from two donors after conditioning. The recipient achieved a complete remission without graft-versus-host disease. Double chimaerism was documented in several leucocyte subpopulations; both units contributed to haematopoiesis until relapse. Triple chimaerism was present from relapse until death due to leukaemia. This approach may potentially improve UCB transplantation outcome for adults lacking a histocompatible donor.
Human Multi-Chimeric Cell (HMCC) Therapy as a Novel Approach for Tolerance Induction in Transplantation. [2023]Cellular therapies are regarded as the most promising approach for inducing transplant tolerance without life-long immunosuppression in solid organ and vascularized composite allotransplantation (VCA). Currently, no therapies are achieving this goal. This study introduces a novel Human Multi-Chimeric Cell (HMCC) line created by fusion of umbilical cord blood (UCB) cells, from three unrelated donors as an alternative therapeutic approach to bone marrow transplantation and tolerance induction in solid organ and VCA transplants. We performed eighteen ex vivo polyethylene glycol mediated fusions of human UCB cells from three unrelated donors to create HMCC. Mononuclear cells labeled with PKH26, PKH67, and eFluor™ 670 fluorescent dyes were fused and sorted creating a new population of triple-labeled (PKH26/PKH67/eFluor™ 670) HMCC. The creation of HMCC from three unrelated human UCB donors was confirmed by flow cytometry and confocal microscopy. Genotyping analyses determined the tri-chimeric state of HMCC by presence of parent alleles and selected loci specific for each of three UCB donors. Phenotype characterization confirmed hematopoietic markers distribution, comparable to UCB donors. HMCC maintained viability and displayed a low apoptosis level. The COMET assay revealed absence of genotoxicity, confirming fusion safety. Colony forming units assay showed clonogenic properties of HMCC. This study confirmed the feasibility of HMCC creation from three unrelated human UCB donors and characterized tri-chimeric state, hematopoietic phenotype, viability, safety, and clonogenic properties of HMCC. The created HMCC line, representing genotype characteristics of three unrelated human UCB donors, introduces a novel therapeutic approach for bone marrow, solid organ, and VCA transplants.
Refining eligibility criteria of unit selection for myeloablative cord blood transplantation in acute leukemia: Real-world experience of a referral center. [2023]The algorithm for cord blood (CB) unit selection is still somewhat ambiguous. We retrospectively analyzed 620 cases of acute leukemia between 2015 and 2020, who were treated with myeloablative single-unit umbilical CB transplantation (UCBT). We found that, when human leukocyte antigen (HLA) mismatch was ≤3/10, CD34+ cell dosage <0.83 × 105/kg-considerably lower than prevalent guidelines-was permissible without affecting survival. Moreover, synergy between donor killer-cell immunoglobulin-like receptors (KIR) haplotypes-B and donor-recipient HLA-C mismatch protected against relapse-related mortality. We submit that minimum required CD34+ cell dosage can possibly be relaxed to broaden access to UCBT, and donor KIR genotyping should be considered during unit selection.
Double umbilical cord blood transplantation: relevance of persistent mixed-unit chimerism. [2015]Double umbilical cord blood transplantation (UCBT) was developed as a strategy to circumvent the cell dose limitation of single UCBT with a concomitant potential benefit of lowering the rate of leukemia relapse. Sustained hematopoiesis after double UCBT usually is derived from a single donor unit, as only a few patients have been reported to display stable mixed-unit chimerism for varying periods of time. Explanations for the 1 unit dominance, predictors for identifying unit superiority, and persistence of long-term mixed-unit chimerism remain elusive. Review of published literature revealed only 11 of 280 patients (4%) with mixed-unit chimerism for at least 1 year after transplantation, with 3 patients receiving reduced-intensity conditioning regimens. Mixed-unit chimerism was more likely if both units were closely HLA matched to each other. Outcome data for patients with stable mixed-unit chimerism, for the most part, were scarcely reported. Analysis of the small sample size revealed a potential advantage of stable mixed-unit chimerism on enhancing the graft-versus-leukemia effect; however, definitive conclusions cannot be made on the effect of mixed-unit chimerism on the rates of graft-versus-host disease. Therefore, gathering outcome data prospectively in larger clinical series will help answer the question of whether stable mixed-unit chimerism is either beneficial and, therefore, should be strived for, detrimental and, thus, needs to be eliminated, or if it is of no clinical consequence.
Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. [2019]Optimizing cord blood donor selection based mainly on cell dose and human leukocyte antigen (HLA) disparities may further improve results of unrelated cord blood transplants (UCBT).
The role of haploidentical stem cell transplantation in the management of children with haematological disorders. [2019]The broader application of stem cell transplantation (SCT) for paediatric diseases has been limited by a lack of human leucocyte antigen (HLA)-matched donors. Virtually all children, however have at least one haploidentical parent who could serve as a donor. Such a donor is immediately available and the considerable costs of additional HLA typing, registry and banking expenditures that are necessary to procure an unrelated donor, could be reduced. Recent technological advances appear to have overcome the historical problems of graft rejection and severe graft versus host disease in the haploidentical setting, and in the latest studies the overall survival for children undergoing haploidentical SCT for leukaemia is now comparable with that following unrelated donor bone marrow or cord blood transplantation. Post-transplant infectious complications and leukaemia relapse remain the most important barriers yet to overcome, and new directions in the use of adoptive cellular immunity appear to be promising in this respect. Haploidentical SCT is now a viable option for those children who do not have an HLA compatible sibling or fully matched unrelated donor. The relative merits of a haploidentical family donor versus mismatched unrelated bone marrow or cord blood donation needs to be assessed in prospective, randomized clinical trials.
[Treatment of two case childhood acute lymphoblastic leukemia by HLA-mismatched unrelated umbilical cord blood transplantation]. [2016]To explore the hematopoietic and immunologic reconstitution and transplantation-related complications of HLA one locus mismatched unrelated umbilical cord blood transplantation for the treatment of hematological malignancies.
Should double cord blood transplants be the preferred choice when a sibling donor is unavailable? [2021]Umbilical cord blood transplant is an important alternative stem cell source for both children and adults with haematologic malignancies. Umbilical cord blood units are rapidly available and have less stringent human leucocyte antigen (HLA) matching requirements. Mismatch at two antigens actually improves the risk of relapse for umbilical cord blood transplant recipients with relatively low risk of severe acute or chronic graft-versus-host disease. However, umbilical cord blood transplant is associated with an inferior neutrophil recovery rate when compared with other stem cell sources. Therefore, we have explored double-unit umbilical cord blood transplants, not only as a platform for evaluating the safety and effectiveness of new methods of ex vivo expansion or methods of enhanced homing, but also as an approach in itself to remedy the problem of limited cell dose, particularly for adults.
Alternate Donor Transplantation. [2023]There is a significant need for alternative donors other than full-matched related or unrelated donors for allogeneic hematopoietic stem cell transplantation, especially in the Asia Pacific, where donor registries are smaller, and ethnicities are far more diverse. Both umbilical cord blood (UCB) and haploidentical transplantation can be carried out despite significant human leukocyte antigen (HLA) mismatches between patients and donors and help to meet this need. There are advantages and disadvantages to UCB and haploidentical transplantation, though enhancements in technology continue to improve outcomes in both. Donor selection for these cell sources is dependent on the presence of donor specific anti-HLA antibodies in the recipient's serum, degree and characteristics of donor-recipient HLA mismatches, ABO compatibility. Specific to haploidentical transplantation, additional factors like donor age, sex, donor-recipient CMV serology as well as NK cell alloreactivity are also important.
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.
Strategies in haploidentical stem cell transplantation in adults. [2021]Haploidentical related donors are alternative stem cell sources for patients without human leukocyte antigen (HLA)-matched related or unrelated donors. Immediate access to the donor, availability for patients with rare haplotypes, ease of stem cell procurement, and lack of a requirement for a physical cord blood bank or an extensive HLA database render this type of hematopoietic stem cell transplantation particularly attractive despite the high histoincompatibility barrier between the recipient and the haploidentical graft. In this review, we answer the following questions: 1) What are the current transplant strategies used to overcome the histoincompatibility barrier in haploidentical stem cell transplantation and their clinical results? 2) How should we choose the donor when there is more than one available haploidentical donor? 3) How does transplantation from haploidentical donors compare to that from umbilical cord blood?
The great debate: haploidentical or cord blood transplant. [2011]One of the truly revolutionary advances in hematopoietic cell transplantation (HCT) is the increasingly successful use of alternative donors, thereby allowing the delivery of a potentially curative transplant to ∼75% of patients who do not have an HLA-matched sibling donor. A substantial proportion of the need has been met by HLA-matched volunteer unrelated donors, but an unmet need still exists, particularly among minority populations and for people who need a more immediate source of hematopoietic cells. Two such sources, umbilical cord blood (UCB) and haploidentical related donors, have filled most of this need, and outcomes following transplants from these donor sources are very promising. UCB has the advantages of ready availability and is less capable of causing GVHD but hematological recovery and immune reconstitution are slow. Haploidentical HCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post transplant cellular immunotherapy, but is complicated by a high risk of GVHD and poor immune reconstitution when GVHD is prevented by vigorous ex vivo or in vivo T-cell depletion. This review will discuss the pertinent issues that affect the choice of one donor source over another and offer recommendations regarding the optimal utilization of these donor sources.
Overview of the progress on haploidentical hematopoietic transplantation. [2020]Allogeneic hematopoietic stem cell transplant (HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLA-matched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor, umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graft-versus-host disease caused by major donor-recipient HLA-disparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.