Trial Summary
What is the purpose of this trial?Cord blood transplants (CBT) are a standard treatment for adults with blood cancers. MSK has developed a standard ("optimized") practice for cord blood transplant (CBT). This optimized practice includes how patients are evaluated for transplant, the conditioning treatment (standard chemotherapy and total body irradiation therapy) given to prepare the body for transplant, the amount of stem cells transplanted, and how patients are followed during and after transplant.The purpose of this study is to collect information about participant outcomes after CBT following MSK's optimized practice. The researchers will look at outcomes of the CBT treatment such as side effects, disease relapse, GVHD, and immune system recovery after CBT treatment.
What safety data exists for cord blood transplant in treating blood cancers?Cord blood transplants, a form of allogeneic hematopoietic stem cell transplantation, have been studied for their safety and efficacy in treating blood cancers. Research indicates that while high-dose conditioning regimens can lead to severe toxicity, less toxic, reduced-intensity conditioning regimens are being developed to improve safety. These regimens aim to reduce procedure-related mortality, which remains high at 10-30%, and improve outcomes such as donor chimerism and event-free survival. Studies have shown that using low-dose total body irradiation and immunosuppressive agents can reduce toxicity. Additionally, supportive care improvements have decreased regimen-related mortality and morbidity, although complications still exist. Overall, ongoing research is focused on developing safer conditioning agents and improving supportive care to enhance the safety of cord blood transplants.234514
Is the treatment 'Conditioning Chemotherapy, Cord blood graft' a promising treatment for blood cancers?Yes, the treatment using cord blood grafts is promising for blood cancers. It offers a good alternative for patients who can't find a matching donor, with similar survival rates to traditional bone marrow transplants. It has been successful in curing many patients and is especially helpful for those from diverse backgrounds who struggle to find a match. The treatment has been widely adopted and continues to show positive results.167811
What data supports the idea that Cord Blood Transplant for Blood Cancers is an effective treatment?The available research shows that Cord Blood Transplant is an effective treatment for blood cancers. It has several advantages over traditional bone marrow transplants, such as better matching and quicker availability. Studies indicate that it leads to a lower chance of a condition called graft-versus-host disease, where the transplanted cells attack the patient's body, and it has a higher ability to fight tumors. Additionally, Cord Blood Transplant has been shown to reduce relapse rates, which means the cancer is less likely to come back, and it offers similar overall survival rates compared to other donor sources. These benefits make it a promising option for patients who cannot find a suitable donor for a bone marrow transplant.89101213
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. However, since the trial involves chemotherapy and total body irradiation, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators or your doctor for specific guidance.
Eligibility Criteria
This trial is for adults with various high-risk blood cancers, including different types of leukemia and lymphoma. Participants must meet specific criteria such as being in a certain phase of remission, having adequate organ function, and not having had certain previous treatments like stem cell transplants within the last year.Treatment Details
The study tests an 'optimized' cord blood transplant (CBT) process developed by MSK. It includes evaluation methods, conditioning chemotherapy, total body irradiation before the transplant, and post-transplant care to assess side effects, disease relapse rates, graft-versus-host disease (GVHD), and immune recovery.
1Treatment groups
Experimental Treatment
Group I: Cord Blood TransplantExperimental Treatment2 Interventions
Adult patients with high-risk hematologic malignancies and a suitable double-unit CB graft will undergo work-up to assess protocol eligibility. CB graft selection will be based on established MSKCC guidelines. Patients will receive standard conditioning with Cy 50 mg/kg, Flu 150 mg/m2, Thio 10 mg/kg, and TBI 400 cGy according to the eligibility criteria. GVHD prophylaxis will consist of CSA and MMF starting day -3. The double-unit CB graft will be infused on day 0 per standard practice. Optimized CBT practices, will be implemented in this protocol.
Conditioning Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Chemotherapy for:
- Blood cancers
- Leukemia
- Lymphoma
- Multiple myeloma
🇺🇸 Approved in United States as Chemotherapy for:
- Blood cancers
- Leukemia
- Lymphoma
- Multiple myeloma
🇨🇦 Approved in Canada as Chemotherapy for:
- Blood cancers
- Leukemia
- Lymphoma
- Multiple myeloma
🇯🇵 Approved in Japan as Chemotherapy for:
- Blood cancers
- Leukemia
- Lymphoma
- Multiple myeloma
🇨🇳 Approved in China as Chemotherapy for:
- Blood cancers
- Leukemia
- Lymphoma
- Multiple myeloma
🇨🇭 Approved in Switzerland as Chemotherapy for:
- Blood cancers
- Leukemia
- Lymphoma
- Multiple myeloma
Find a clinic near you
Research locations nearbySelect from list below to view details:
Memorial Sloan Kettering Monmouth (Consent only)Middletown, NJ
Memorial Sloan Kettering Nassau (Consent only)Uniondale, NY
Memorial Sloan Kettering Cancer CenterNew York, NY
Memorial Sloan Kettering Bergen (Consent only)Montvale, NJ
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Who is running the clinical trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
[Present state of cord-blood stem cell transplantation]. [2007]Allogeneic bone marrow transplantation (BMT) can cure some hematologic and solid malignancies, but its success depends on the prompt identification of a suitable donor and the avoidance of severe graft-versus-host (GVH) disease. Transplantation using hematopoietic stem cells from umbilical cord blood may overcome these problems. Over the past several years, cord blood transplantation (CBST) from siblings and unrelated donors has been performed in more than 300 patients. The probability of event-free survival was almost similar to that for BMT. This review described the recent status of CBST in USA, Europe and Japan, and the outlook for CBST.
[Patient treated with chemotherapy. Alarm signs requiring immediate intervention]. [2006]The most common complications in patients receiving chemotherapy are neutropenia with fever, and infections. The risk-adapted application of antibodies, antimycotics and G-CSF is discussed. Nausea and vomiting can usually be avoided by appropriate prophylactic antiemetic treatments. Less common are thrombocytopenia requiring replacement treatment. The frequent anemias associated with tumor treatment have a multifactorial genesis. Red cell concentrates and, where indicated, erythropoietin are available. Typical organ-related side effects of cytostatic agents are rare, but then usually serious. Problems with veins may be resolved with "undertunneled" central venous catheters or completely implanted port systems.
Aims of conditioning. [2019]Nuclear warfare research and treatment of radiation accident victims uncovered the potential of hemopoietic stem cell transplants. Prior to transplantation of hemopoietic stem cells patients receive "conditioning" agents: high-dose total-body irradiation and/or high-dose chemotherapy. High-dose conditioning causes at least 20% procedure-related mortality. Recent efforts to reduce procedure-related mortality by the use of low-dose conditioning included low-dose total-body irradiation, immunosuppressive agents, and the replacement of high-dose chemotherapy by donor lymphocytes for graft-vs-tumor effects. Procedure-related mortality remains high (10-30%). Tumor recurrence at 1 year is over 50%. In this review, the aims of conditioning (creation of space, prevention of hemopoietic stem cell rejection, eradication of immune memory, and eradication of tumor cells) are reexamined in those patient and animal studies that explore quantitative and mechanistic conditioning issues. Translational experimental animal models provide the best opportunities for the development of less toxic conditioning agents for human patients and require an analysis of the consequences of the effects of new conditioning agents on host-vs-graft as well as graft-vs-host reactions. Total-body irradiation or other forms of radiation create space, prevent rejection of histocompatible stem cells, and can eliminate immune memory to autoimmune antigens at modest, nontoxic doses. The transplantation of histoincompatible stem cells and the eradication of large loads of tumor cells remain problematic. The therapeutic index of allogeneic stem cell transplants will increase if new conditioning agents are targeted only to those host tissues that need conditioning: hemopoietic system, immune system, and tumor masses. Radiolabeled immunoglobulins are among the most promising new, low-toxicity conditioning agents.
Low dose total body irradiation followed by allogeneic lymphocyte infusion for refractory hematologic malignancy--an updated review. [2019]Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy and radiotherapy used in conventional myeloablative conditioning regimens may lead to severe toxicity. In our initial study, we treated 25 patients with refractory cancers with 100 cGy total body irradiation (TBI) followed by allogeneic, non mobilized peripheral blood cells. Eighteen patients received sibling and 7 patients received unrelated cord blood stem cells. None of the 13 patients with solid tumors achieved donor chimerism or had a sustained response. Twelve patients with hematologic malignancies were treated, 1 received a cord blood transplant and 11 received sibling donor cells. Nine of these 11 patients achieved donor chimerism, ranging from 5% to 100%. Four patients had sustained complete remission of their cancers, and 2 are long-term survivors. The development of chimerism correlated with total previous myelotoxic chemotherapy (p
Managing the toxicity of hematopoietic stem cell transplant. [2005]Hematopoietic stem cell transplant is an established treatment modality for a variety of neoplastic, hematologic, and immunologic disorders. Fueled in part by remarkable technologic advances, the number of both autologous and allogeneic transplants has increased dramatically over the past decade. Peripheral blood stem cells have largely replaced bone marrow as the source of hematopoietic progenitors in autologous transplants, and their use in the allogeneic setting has increased substantially. Less toxic transplants, in the form of non-myeloablative conditioning regimens, are being actively investigated, with the promise of expanding indications and age limits for allogeneic transplant. A successful global infrastructure allowing sharing of HLA-typing information has led to increased availability of non-sibling, HLA-matched, unrelated donor transplants for many patients who lack a suitable sibling donor. Finally, umbilical cord blood transplants are being investigated in both children and adult patients. The ability to transplant more individuals with broader indications owes much to a concurrent improvement in supportive care agents and techniques. Although regimen-related mortality and morbidity have decreased, stem cell transplants continue to pose multiple potential complications. A careful proactive assessment to identify, treat, and, hopefully, prevent adverse events is essential to a successful transplant. This review is intended to summarize some of the toxicities of hematopoietic stem cell transplant in a systematic, organ-based fashion and to review the treatment options available for each of these side effects.
Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. [2013]We conducted a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies. Seventeen patients with a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17-28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT using a non-TBI regimen in adults. When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect. Further studies are required to identify patients who benefit from this regimen.
Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. [2021]We studied the clinical outcomes of 171 adults with hematologic malignancies who received unrelated cord blood transplantation (CBT) as a primary unrelated stem-cell source (n=100), or bone marrow transplant (BMT) or peripheral blood stem-cell transplant (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT). All patients received myeloablative regimens including 12 Gy total body irradiation. We analyzed the hematologic recovery, and risks of graft-versus-host disease (GVHD), transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. Significant delays in engraftment occurred after cord blood transplantation; however, overall engraftment rates were almost the same for both grafts. The cumulative incidences of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients were significantly lower than those among BMT/PBSCT recipients. Multivariate analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data suggest that unrelated cord blood could be as safe and effective a stem-cell source as related bone marrow or mobilized peripheral blood for adult patients when it is used as a primary unrelated stem-cell source.
Cord blood transplantation: evolving strategies to improve engraftment and immune reconstitution. [2019]For many patients with relapsed or high-risk hematologic malignancies, allogeneic stem cell transplantation offers the best hope for cure. For patients lacking a suitable family or unrelated donor, umbilical cord blood provides a promising alternative graft source. Dramatic advances in cord blood transplantation (CBT) have been made in the past 2 decades, leading to a rapid expansion of CBT programs worldwide.
[Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies]. [2012]To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies.
Umbilical cord blood transplantation: a maturing technology. [2016]The use of umbilical cord blood (CB) as a source of hematopoietic progenitor cells for patients with high-risk hematologic disorders receiving allogeneic hematopoietic cell transplantations (HCTs) has increased significantly. Single-institution and registry studies have shown a decreased relapse rate and an increased transplantation-related mortality rate with similar overall survival rates after allogeneic HCT with CB compared with other donor sources. The transplantation of double CB units has overcome the dose limitation inherent in a single CB unit and thus has markedly extended the use of CB to larger children and adults. Similarly, the use of reduced intensity conditioning in the CB transplantation setting has allowed the treatment of older patients who would be unable to tolerate the myeloablative regimens used in the original CB transplantation protocols.
Update on umbilical cord blood transplantation. [2019]Allogeneic hematopoietic cell transplant is a curative procedure for many patients with leukemia, lymphoma, myelodysplasia, myeloproliferative neoplasms, and genetic disorders. Umbilical cord blood transplantation is a graft source for patients who do not have a matched donor in their family or in the unrelated registry. It is particularly difficult for Black, Hispanic, and White patients of non-Western European background to find fully matched adult volunteer donors. An estimated 700,000 umbilical cord blood units have been donated for public use, and over 40,000 umbilical cord blood transplantations have been performed. Over 25,000 patients have been cured with this approach.
Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives. [2019]Hematopoietic cell transplantation is a potentially lifesaving procedure for patients with hematological malignancies who are refractory to conventional chemotherapy and/or irradiation treatment. Umbilical cord blood (CB) transplantation, as a hematopoietic stem and progenitor cell (HSPC) source, has several advantages over bone marrow transplantation with respect to matching and prompt availability for transplantation. Additionally, CB has some inherent features, such as rapid expansion of T cells, lower prevalence of graft-versus-host disease and higher graft versus tumor efficacy that make this HSPC cell source more favorable over other HSPC sources. Areas covered: This review summarizes the current CB and CB derived T cell applications aiming to better disease control for hematological malignancies and discusses future directions to more effective therapies. Expert commentary: CB transplantation could be used as a platform to extract cord blood derived T cells for ex vivo expansion and/or gene modification to improve cellular immunotherapies. In addition, combining cord blood gene-engineered T cell products with vaccination strategies, such as cord blood derived dendritic cell based vaccines, may provide synergistic immunotherapies with enhanced anti-tumor effects.
Conditioning with 10 Gy Total Body Irradiation, Cyclophosphamide, and Fludarabine without ATG Is Associated with Improved Outcome of Cord Blood Transplantation in Children with Acute Leukemia. [2021]The optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia.
Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children. [2022]Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m2, melphalan (MEL) 210 mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.