Track topics on Twitter Track topics that are important to you
This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB) Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible without conferring grade II-IV acute graft-versus-host disease (GVHD).
In this study, the investigators propose to add UCB Treg and UCB CD3+ Teff cells to the two TCD UCB donor units with the goal of transplanting as many CD3+ Teff cells as possible without reintroducing risk of acute GVHD. The investigators hypothesize that Treg will permit the reintroduction of CD3+ Teff cells that will provide a bridge while awaiting HSC T cell recovery long term. The co-infusion of Treg will prevent GVHD without the need for prolonged pharmacologic immunosuppression.
Based on prior studies, the first patient will start at lowest dose combination (3 x 10^6/kg of Treg and 3 x 10^6/kg of CD3+ Teff cells). One patient will be entered at each level with a minimum of 35 days to observe the patient prior to moving to the next dose level. (1) If GVHD does not occur, a "successful step", then the CD3+ Teff cell dose will increase to the next higher level for the next patient; (2) If GVHD occurs, a "failed step", then Treg dose will increase to the next higher level for the next patient. It would take a minimum of 5 (if no GVHD) and maximum of 9 patients (if GVHD is observed at each level) to complete all Treg:CD3+ Teff cell combinations.
An additional 10 patients will be enrolled to verify that this reflects the optimal combination and evaluate its safety profile.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Treg cells, CD3+ Teff cells, Fludarabine, Cyclophosphamide, Total body irradiation, Umbilical cord blood transplantation
Masonic Cancer Center, University of Minnesota
Not yet recruiting
Masonic Cancer Center, University of Minnesota
Published on BioPortfolio: 2014-08-27T03:12:11-0400
This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used...
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of...
The purpose of this research study is to: (1) determine if the combination of low dose total body irradiation, low dose cyclophosphamide and the addition of fludarabine, and a serum to sup...
Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Immunodeficiency or Noncancerous Inherited Disorders
RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immun...
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them ...
Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to ...
A progressive waning in Foxp3(+) regulatory T (Treg) cell function provokes autoimmunity in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D), a cellular defect rescued by prophylactic...
A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the...
Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated w...
CD4+ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4+ T effector (Teff) cel...
Multinucleated cells (fused macrophages) seen in granulomatous inflammations such as tuberculosis, syphilis, sarcoidosis, and deep fungal infections. They resemble foreign-body giant cells (GIANT CELLS, FOREIGN BODY) but Langhans giant cells contain less chromatin and their nuclei are arranged peripherally in a horseshoe-shaped pattern. Langhans giant cells occur frequently in delayed hypersensitivity.
Multinucleated cells (fused macrophages), characteristic of granulomatous inflammation, which form around exogenous material in the skin. They are similar in appearance to Langhans giant cells (GIANT CELLS, LANGHANS), but foreign-body giant cells have more abundant chromatin and their nuclei are scattered in an irregular pattern in the cytoplasm.
Histiocytic, inflammatory response to a foreign body. It consists of modified macrophages with multinucleated giant cells, in this case foreign-body giant cells (GIANT CELLS, FOREIGN-BODY), usually surrounded by lymphocytes.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
Cells forming a framework supporting the sensory AUDITORY HAIR CELLS in the organ of Corti. Lateral to the medial inner hair cells, there are inner pillar cells, outer pillar cells, Deiters cells, Hensens cells, Claudius cells, Boettchers cells, and others.
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...