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

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:
NCT00082329
First received: May 6, 2004
Last updated: February 8, 2013
Last verified: October 2012
  Purpose

This 12-day study will test whether the combination of C-CSF (granulocyte-colony stimulating factor) and AMD3100 is more efficient in mobilizing stem cells for collection than the use of G-CSF alone. Traditionally, the growth factor G-CSF has been given to stem cell donors to mobilize, or push, stem cells out of the bone marrow and into the blood circulation for collection for transplantation. Although a sufficient quantity of cells usually can be collected with G-CSF treatment, some donors do not respond well and may require multiple apheresis procedures (see below) to collect enough cells. Studies indicate that G-CSF used together with a drug called AMD3100 may be more effective in mobilizing stem cells for collection than G-CSF alone. The Food and Drug Administration has approved C-CSF for stem cell mobilization. AMD3100 is a new drug that also mobilizes stem cells in large numbers within a few hours.

Normal healthy volunteers between 18 and 60 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, and electrocardiogram (EKG).

Participants undergo the following tests and procedures:

Day 1:

  • Blood draw for clinical monitoring and for research studies
  • Baseline abdominal ultrasound to measure spleen size
  • C-CSF injection under the skin

Days 2 and 3:

- G-CSF injections under the skin

Day 4:

  • G-CSF injection
  • Blood draw for clinical monitoring and for research studies
  • Abdominal ultrasound to monitor for changes in spleen size
  • AMD3100 injection in the abdomen, arm, or thigh

Day 5:

  • G-CSF injection
  • Blood draw for clinical monitoring and for research studies
  • Apheresis to collect stem cells. For this procedure, a catheter (plastic tube) is placed in a vein in each arm. Blood is withdrawn from one vein and circulated through a cell separator machine, which collects and saves stem cells and lymphocytes (a type of white blood cell) and returns the rest of the blood to the subject through the catheter in the vein in the other arm. The collected stem cells are not given to a patient, but are examined in the laboratory to see if they are suitable for transplant.
  • Blood draw to monitor for side effects
  • EKG
  • Abdominal ultrasound to monitor for changes in spleen size

Days 10 through 12:

  • Telephone follow-up for review of symptoms
  • Blood draw to monitor for treatment side effects

Condition Intervention Phase
Healthy
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 Using Granulocyte Colony Stimulating Factor (G-CSF) Combined With AMD3100 in Healthy Volunteers

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To determine the cytokine polarization status of CD4+ T-cells collected by apheresis following combination of AMD3100 and G-CSF compared to G-CSF mobilization. [ Time Frame: Day 1 (cells are counted 24 hours after AMD3100) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To examine 1) the cellular content and other immune properites of mobilized cells; 2) yields of hematopoietic prognitor 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: 9
Study Start Date: May 2004
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: AMD3100
    N/A
Detailed Description:

Peripheral blood progenitor cells (PBPC) are the most popular source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and faster 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% of the donors will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. AMD3100 reversibly inhibits CXCR4 binding to stromal cell derived factor (SDF) - 1 and was recently discovered to be an effective agent to mobilize CD34+ cells into the peripheral blood. In normal volunteers, administering AMD3100 after 4-5 days of G-CSF resulted in a 3-3.5 fold increase in circulating CD34 cells compared to G-CSF alone. Recent data has suggested that the combination of G-CSF and AMD3100 is superior to G-CSF alone for mobilizing hematopoietic progenitor cells in heavily pretreated patients with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous hematopoietic transplantation. Combining AMD3100 with G-CSF could be an effective strategy to improve the yield of PBPC collected from allogeneic donors who mobilize poorly with G-CSF alone. However, the biological impact of AMD3100 in this context on T cells and other cellular populations contained within the allograft that mediate GVHD and graft-versus-leukemia (GVL) effects are unknown.

We propose to collect PBPC from healthy volunteers following 5 days of G-CSF (10 mcg/kg/day) and a single dose of AMD3100 (240 mcg/kg subcutaneous given 12 hours before starting apheresis) to study the impact of combining these two mobilizing agents on the immunological properties of the mobilized cells. A single 15 liter apheresis will be conducted on day 5 following the 5th dose of G-CSF. The immunological studies conducted on these mobilized cells will be the same as our parallel study which is investigating the immune properties of PBPCs mobilized with G-CSF or AMD3100 alone. If combining AMD3100 with G-CSF has no negative impact on the immune populations involved in GVHD and graft-vs-leukemia effects, this regimen could be used for allogeneic donors who fail to mobilize sufficient PBSC using G-CSF alone.

Primary objective: To determine the cytokine polarization status of CD4+ T-cells collected by apheresis following combination of AMD3100 and G-CSF compared to G-CSF mobilization.

Primary endpoint: the ratio of Th1 (intracellular IFN-g +) versus Th2 (intracellular IL-4+) T-cells in the apheresis products collected from individual donors undergoing mobilization with combination of G-CSF and AMD3100 to the ratio in apheresis product collected with G-CSF alone (ratio published in literature).

Secondary endpoints: To examine 1) the cellular content and other immune properties of mobilized cells; 2) yields of hematopoietic progenitor cells, immune cells, and other cellular subsets collected by apheresis; and the 3) safety profile of AMD3100.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Healthy volunteers greater or equal to 18 years old, less than or equal to 60 years.

Weight greater than 60 kg (132 pounds)

Normal renal function: creatinine less than 1.5 mg/dl l

Normal liver function: bilirubin less than1.5mg/dl, transaminases within normal limit

Normal blood count: WBC 3000-10000/mm3, granulocytes greater than 1500/mm3, platelets greater than 150,000/mm3, hemoglobin greater than 12.5g/dl

Subject must be eligible for normal blood donation and fit to undergo apheresis procedure (antecubital veins must be adequate for peripheral access during apheresis)

Ability to comprehend the investigational nature of the study and provide informed consent

EXCLUSION CRITERIA: any of the following

Active infection or history of recurrent infection or positive test for syphilis (RPR), hepatitis B and C (HBaSAg, Anti-HCV), HIV and HTLV-1

History of autoimmune disease such as rheumatoid arthritis, systemic lupus erythematous

History of cancer within the past 5 years excluding basal cell or squamous cell carcinoma of the skin

History of any hematologic disorders including thromboembolic disease

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 CHD risk

History of heavy smoking with underlying pulmonary disease

History of cerebrovascular disease, transient ischemic attack, or stroke

Diagnosis of sickle cell anemia or sickle cell trait (to be screened by Hbg electrophoresis)

Pregnant or lactating

Severe psychiatric illness: mental deficiency sufficiently severe as to make informed consent impossible.

Mobilization with G-CSF within 90 days of protocol enrollment.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00082329

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: NCT00082329     History of Changes
Other Study ID Numbers: 040179, 04-H-0179
Study First Received: May 6, 2004
Last Updated: February 8, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hematopoietic Stem Cells
PBSC's
Mobilization
Alloreactivity
T Cell Polarization
Dendritic Cells
CXCR4
Plerixafor
Healthy Volunteer
HV

Additional relevant MeSH terms:
Lenograstim
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014