Safety of a Single Dose of 5 mg of hLF1-11 Given to Autologous Haematopoietic Stem Cell Transplant Recipients
Summary
The safety and tolerability of hLF 1-11 has to be established first in HSCT recipients who are at risk of developing, but have not yet developed, infectious complications due to invasive fungal disease. These patients are different from healthy volunteers because they have received myeloablative treatment which not only arrests haematopoiesis resulting in neutropenia but also induces mucosal barrier injury both of which predispose to infections which typically occur during the week after transplant. It is therefore essential to know that hLF 1-11 is when given during neutropenia and mucosal barrier injury before infections ensue
Description
Background:
Human lactoferrin (hLF) is a glycoprotein containing 692 amino acids and found in the saliva, milk, tears, and other body fluids. Peptide representing the first cationic domain, i.e. a peptide comprising the first eleven residues of hLF (further referred to as hLF1-11) was significantly more effective than the full length hLF or the peptide representing the second cationic domain in killing a variety of bacteria in vivo. The mechanism of action comprises a number of independent factors. The classical way to explain the efficacy is the direct killing effect, which typically is observed in vitro at relatively high concentrations. The results of in vitro and in vivo experiments suggest that the mechanism of action is predominantly through the intermediary of cells and/or components of the host as opposed to a direct interaction with the pathogen.
The objective is to develop hLF1-11 as an effective and safe antibacterial and antifungal for the treatment of fungal and bacterial infections that develop during the neutropenia that results from myeloablative therapy to prepare for a haematopoietic stem cell transplant (HSCT) formerly referred to as bone marrow transplant. Rates of infection and related morbidity are high in this population making it an attractive target for testing clinically the proof-of-principle that hLF1-11 can provided effective treatment. Subsequently, hLF1-11 will be developed further as a systemic antifungal agent.
Study Design
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Conditions
Hematopoietic Stem Cell Transplantation
Intervention
human lactoferrin peptide 1-11
Location
UMC St. Radboud
Nijmegen
Gelderland
Netherlands
6500 HB
Status
Completed
Source
AM-Pharma
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00509938
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Hematopoietic Stem Cell Transplantation
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
Bone Marrow Transplantation
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
Hematopoietic Stem Cell Mobilization
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
Cord Blood Stem Cell Transplantation
Transplantation of STEM CELLS collected from the fetal blood remaining in the UMBILICAL CORD and the PLACENTA after delivery. Included are the HEMATOPOIETIC STEM CELLS.
Peripheral Blood Stem Cell Transplantation
Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.
Clinical Trials
Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus
The purpose of this study is to determine if autologous nonmyeloablative hematopoietic stem cell transplantation is able to induce prolonged and significant increases of C-peptide levels a...
Hematopoietic Stem Cell Transplantation for the Treatment of Limb Ischemia and Diabetic Neuropathy
Several pathophysiological theories have been proposed for the development of diabetic chronic complications. In recent years, the use of stem cells (totipotential, hematopoietic or endoth...
The purpose of this study is to establish the tolerability of treatment with human lactoferrin 1-11 peptide (hLF1-11) administered intravenously as a single dose given for 10 consecutive d...
This is a perspective multicentric study for the treatment of patients aged equal or less than 60 years and submitted to an allogeneic hematopoietic stem cell transplantation from an HLA c...
The objectives of this study are as follows: To demonstrate the safety of escalating doses of opebacan in subjects undergoing myeloablative allogeneic Hematopoietic Stem Cell Transplantat...
PubMed Articles
Late effects on haemostasis after haematopoietic stem cell transplantation.
Allogeneic and autologous hematopoietic stem cell transplantations are important therapeutic options for patients with hematologic disorders. Hemostatic complications are frequent after hematopoietic...
Cord Blood Stem Cells for Hematopoietic Transplantation.
Cord blood (CB) is an important alternative source of hematopoietic stem cells (HSCs) for transplantation today. The principal drawbacks of cord blood transplantation are the limited number of hematop...
Expansion of human cord blood hematopoietic stem cells for transplantation.
A recent Science paper reported a purine derivative that expands human cord blood hematopoietic stem cells in culture (Boitano et al., 2010) by antagonizing the aryl hydrocarbon receptor. Major probl...
Duodenal leishmaniasis after allogeneic hematopoietic SCT.
Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation.
OBJECTIVE: Hematopoietic stem cells are kept in a quiescent state in the hypoxic area of the bone marrow, which is essential for hematopoietic stem cell maintenance. However, when and how HSCs acquire...
