Advertisement

Topics

T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

2014-08-27 03:12:11 | BioPortfolio

Summary

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.

Description

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Hematologic Malignancy

Intervention

Treg cells, CD3+ Teff cells, Fludarabine, Cyclophosphamide, Total body irradiation, Umbilical cord blood transplantation

Location

Masonic Cancer Center, University of Minnesota
Minneapolis
Minnesota
United States
55445

Status

Not yet recruiting

Source

Masonic Cancer Center, University of Minnesota

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:11-0400

Clinical Trials [8425 Associated Clinical Trials listed on BioPortfolio]

Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

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...

Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases

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...

Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine

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...

Fludarabine and Cyclophosphamide Followed By LMB-2 Immunotoxin in Treating Patients With Hodgkin's Lymphoma

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 ...

PubMed Articles [31997 Associated PubMed Articles listed on BioPortfolio]

Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis.

Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effe...

Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation.

Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting pathogenic proliferation of smooth muscle cells. In...

Regulatory T Cell-Mediated Tissue Repair.

Regulatory T-cells (Treg cells) are a specific group of T-cells that maintain immune homeostasis by counteracting the immune responses of conventional T-cells. So far, the therapeutic applications of ...

Defective Treg response in acute kidney injury was caused by a reduction in TIM-3 Treg cells.

Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and bett...

Effector T Cell Resistance to Suppression and STAT3 Signaling during the Development of Human Type 1 Diabetes.

Dysregulation of regulatory T cell (Treg)-mediated suppression and, in particular, resistance of CD4 effector T cells (Teffs) to suppression have been implicated in the pathogenesis of human type 1 di...

Medical and Biotech [MESH] Definitions

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.

More From BioPortfolio on "T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topic

Transplantation
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 ...


Searches Linking to this Trial