AMD3100 to Mobilize Stem Cells for Donation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
ClinicalTrials.gov Identifier:
NCT00075335
First received: January 8, 2004
Last updated: December 8, 2012
Last verified: July 2012
  Purpose

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 CXCR4. CXCR4 is present on CD34+ hematopoetic 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. EBV, 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.


Condition Intervention Phase
Healthy
Blood Component Removal
Drug: AMD3100
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Peripheral Blood Hematopoietic Progenitor Cell Mobilization With AMD 3100 in Healthy Volunteers Previously Mobilized With G-CSF

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine the CD34 plus cell content of an AMD3100 mobilized PBPC in comparison to G-CSF mobilized PBPC from the same healthy donor. [ Time Frame: Day 1 (cells are counted over 24 hours after AMD3100) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1) Determine the CD34 plus cell mobilization kinetics following subcutaneous dose of AMD3100. 2) Yields of hematopoietic progenitor cells, immune cells, and other cellular subsets collected by apheresis; and 3) safety profile of AMD3100. [ Time Frame: Through day 7 ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: January 2004
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: AMD3100
    N/A
Detailed Description:

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. EBV, 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 cellular content and immunological properties of an AMD3100 mobilized PBPC in donors who have previously under gone mobilization with G-CSF, and to further study its safety and efficacy as a peripheral blood stem cell mobilizer.

The primary endpoint is the ratio of Th1 (intracellular IFN-gamma plus) versus Th2 (intracellular IL-4 plus) T-cells in the apheresis products collected from individual donors undergoing G-CSF and AMD3100 hematopoietic progenitor cell mobilization.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • 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 than1.5mg/dl, ALT 6 -41 U/L, AST 9-34 U/L.
    5. Normal blood count: WBC 3000-10000/mm(3)

      granulocytes greater than 1500/mm(3)

      platelets greater than150,000/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: Any of the Following

  1. Active infection or history of recurrent infection- hepatitis B and C (HBsAg, Anti-HBc, Anti-HCV), HIV and 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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00075335

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Richard W Childs, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
ClinicalTrials.gov Identifier: NCT00075335     History of Changes
Other Study ID Numbers: 040078, 04-H-0078
Study First Received: January 8, 2004
Last Updated: December 8, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hematopoietic Stem Cells
Mobilization
Alloreactivity
T Cell Polarization
Dendritic Cells
Plerixafor
Mozobil
Healthy Volunteer
HV

Additional relevant MeSH terms:
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014