AMD 3100 (Mozobil Plerixafor) to Mobilize Stem Cells for Donation

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2012-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be associated with bone pain, headache, myalgia and rarely life threatening side effects like stroke, myocardial infarction and splenic rupture.

AMD3100, is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXC- chemokine receptor 4 (CXCR4). CXCR4 is present on cluster of differentiation 34 (CD34)+ hematopoetic progenitor cells and its interaction with stromal cell derived factor 1 (SDF-1) plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis.

Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization.

In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes, natural killer (NK) cells, and antigen presenting cells. AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

G-CSF and AMD3100 to Mobilize Stem Cells in Healthy Volunteers

NCT00082329

Healthy

COMPLETED PHASE2

AMD3100 (Plerixafor) With G-CSF in Poor Mobilizing Adult Patients Who Previously Failed Hematopoietic Stem Cell (HSC) Collection/Attempts

NCT00396331

Autologous Stem Cell Transplantation

COMPLETED PHASE2

Access Program for Use of AMD3100 to Increase Peripheral Blood Stem Cells for Transplantation in Patients Who Have Failed Standard Therapy Stem Cell Mobilization

NCT00291811

Autologous Stem Cell Transplant

APPROVED_FOR_MARKETING

Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells

NCT01174108

Severe Aplastic Anemia MDS (Myelodysplastic Syndrome)

RECRUITING PHASE2

Alteration in Timing of Plerixafor Administration

NCT01149863

Autologous Transplantation

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoietic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be associated with bone pain, headache, myalgia and rarely life threatening side effects like stroke, myocardial infarction and splenic rupture.

AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. CXCR4 is present on CD34+ hematopoietic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis. Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization. Although the study population is relatively small, side-effects to this agent have been mild and transient with no serious complications having been reported. The ability to collect a large quantity of PBPC with a single injection of this drug makes this an attractive agent for mobilizing donors of allogeneic PBPC. However, the immunologic profiles of AMD3100 mobilized cells, in terms of lymphocyte content (T cell, B cell, NK cell, immuno-regulatory T cell), T cell polarization status (TH1 versus TH2), status of antigen presenting cells (DC1 versus DC2), alloreactive potential, and preservation of reactivity to infectious agents \[e.g. Epstein Barr Virus (EBV), Cytomegalovirus (CMV)\] are unknown. Consequently, whether AMD3100 mobilized PBPC would be suitable for use as an allograft is uncertain. In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes, NK cells, and antigen presenting cells. AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes.

The primary objective is to characterize the immunological properties of AMD3100 mobilized (cytokine gene expression profiles) T-cells compared to G-CSF mobilized T-cells.

Secondary endpoints include the cellular content and other immune properties of AMD3100 mobilized cells yields of hematopoietic progenitor cells, immune cells, and other cellular subsets collected by apheresis in subjects undergoing G-CSF and AMD3100 mobilization and the safety profile of AMD3100.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

AMD 3100 (Mozobil plerixafor)

AMD 3100 (Mozobil plerixafor)mobilized peripheral blood hematopoietic progenitor cells from healthy volunteers will be characterized by cellular content and immunological properties.

Group Type EXPERIMENTAL

AMD3100 (Mozobil plerixafor)

Intervention Type DRUG

AMD 3100 (Mozobil plerixafor)mobilized peripheral blood hematopoietic progenitor cells from healthy volunteers will be characterized by cellular content and immunological properties.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

AMD3100 (Mozobil plerixafor)

AMD 3100 (Mozobil plerixafor)mobilized peripheral blood hematopoietic progenitor cells from healthy volunteers will be characterized by cellular content and immunological properties.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Mozobil plerixafor

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Mobilization and collection of PBPC using G-CSF at least 60 days prior to protocol enrollment (stem cell donors enrolled on Branch transplant protocols or healthy volunteers enrolled on 96-H-0049: Use of granulocyte colony stimulating factor mobilized leukapheresis collections from healthy volunteers).
2. Ages greater than or equal to 18 years and less than or equal to 80 years.
3. Normal renal function: creatinine less than 1.5 mg/dl.
4. Normal liver function: total bilirubin less than 1.5mg/dl, alanine aminotransferase (ALT) 6 -41 U/L, aspartate aminotransferase (AST) 9-34 U/L.
5. Normal blood count: white blood cell (WBC) 3000-10000/mm(3)

granulocytes greater than 1500/mm(3)

platelets greater than 150,000/mm(3)

hemoglobin (females greater than 11.1 g/dl, males greater than 12.7 g/dl).
6. Subject must be eligible for normal blood donation and fit to undergo apheresis procedure (antecubital veins must be adequate for peripheral access during apheresis).
7. Ability to comprehend the investigational nature of the study and provide informed consent.

Exclusion Criteria

1. Active infection or history of recurrent infection- hepatitis B and C (HBsAg, Anti-HBc, Anti-HCV), HIV and human T- lymphocytic virus (HTLV-1).
2. History of autoimmune disease such as rheumatoid arthritis, systemic lupus erythematous.
3. History of cancer within the past 5 years excluding basal cell or squamous cell carcinoma of the skin.
4. History of any hematologic disorders including thromboembolic disease.
5. History of cardiac disease such as uncontrolled hypertension, peripheral vascular disease, myocardial infarction, cardiac arrhythmias OR related symptoms such as tachycardia, chest pain, shortness of breath which have required medical intervention OR treatment or a Framingham coronary disease risk prediction score of greater than 10% 10 year coronary heart disease (CHD) risk.
6. History of cerebrovascular disease, transient ischemic attack, or stroke.
7. Pregnant or lactating.
8. Severe psychiatric illness: mental deficiency sufficiently severe as to make informed consent impossible

Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes