Protocol Number: 04-H-0179

Title:

Peripheral Blood Hematopoietic Progenitor Cell Mobilization Using Granulocyte Colony Stimulating Factor (G-CSF) Combined With AMD3100 in Healthy Volunteers

Number:

04-H-0179

Summary:

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 Blood is withdrawn from one vein and circulated through a cell separator machine, which collects and saves stem cells and lymphocytes (a type of white blood cell) and returns the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

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

Healthy volunteers greater or equal to 18 years old, but 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

No history of chest pain, uncontrolled hypertension, myocardial infarction, peripheral vascular disease, transient ischemic attack, or stroke

No active infection or history of recurrent infection or positive test for syphilis (RPR), hepatitis B and C (HBsAg, Anti-HBc, Anti-HCV), HIV and HTLV-1

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

Female subjects of childbearing age must have a negative urine pregnancy test within one week of beginning G-CSF administration.

Female subjects should not be lactating.

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

EXCLUSION CRITERIA: any of the following

Age less than 18 years or more than 60 years

Pregnant or lactating

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

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

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

History of cardiac disease or related symptoms such as tachycardia, chest pain, shortness of breath, history of cerebrovascular disease. A Framingham Coronary Disease Risk Prediction Score based on LDL cholesterol level will be calculated for each subject. Men with score above 6 and women with score above 10 will be excluded from the study

Peripheral vascular disease

Treatment with G-CSF and/or apheresis procedure within 90 days of protocol enrollment.

Special Instructions: Currently Not Provided

Keywords:

Hematopoietic Stem Cells

PBSC's

Mobilization

Alloreactivity

Recruitment Keywords:

Healthy Volunteer

HV

Conditions:

Healthy

Investigational Drug(s):

AMD3100

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Gyger M, Stuart RK, Perreault C.

Immunobiology of allogeneic peripheral blood mononuclear cells mobilized with granulocyte-colony stimulating factor.

Bone Marrow Transplant. 2000 Jul;26(1):1-16. Review.

PMID: 10918400

Bellucci R, De Propris MS, Buccisano F, Lisci A, Leone G, Tabilio A, de Fabritiis P.

Modulation of VLA-4 and L-selectin expression on normal CD34+ cells during mobilization with G-CSF.

Bone Marrow Transplant. 1999 Jan;23(1):1-8.

PMID: 10037043

Mohle R, Murea S, Kirsch M, Haas R.

Differential expression of L-selectin, VLA-4, and LFA-1 on CD34+ progenitor cells from bone marrow and peripheral blood during G-CSF-enhanced recovery.

Exp Hematol. 1995 Dec;23(14):1535-42.

PMID: 8542944

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