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Protocol Details

Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

94-I-0073

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 2
Max Age: 70

Referral Letter Required

No

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Chronic Granulomatous Disease;
Apheresis;
CD34 Cells;
Infection;
Nadph Oxidase

Recruitment Keyword(s)

Normal Volunteer

Condition(s)

Chronic Granulomatous Disease;
Healthy;
Immunologic Disease;
Leukocyte Adhesion Deficiency Syndrome;
Severe Combined Immunodeficiency

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Allergy and Infectious Diseases

This protocol is designed to study the techniques needed to develop gene therapy or other treatments for certain inherited immune system diseases.

Healthy normal volunteers between 18 and 65 years of age and patients with chronic granulomatous disease (CGD), X-linked severe combined immune deficiency (X-SCID), leukocyte adhesion deficiency (LAD), interferon gamma receptor deficiency (IGR-deficiency) or other inherited diseases affecting precursor blood cells bone marrow cells that generate blood cells may be eligible for this study. Patients who have had repeated severe infections possibly due to an inherited blood cell abnormality may also participate. Candidates will be screened with a medical history, physical examination and blood tests.

Patients with an active infection will be hospitalized during this study. Uninfected participants will be seen as outpatients at the NIH Clinical Center. Participants will have the following procedures:

- G-CSF administration All participants will have daily injections of granulocyte-colony stimulating factor (G-CSF). This drug is a genetically engineered hormone that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream. The injections are given under the skin in the arm or leg, using a very small needle. Patients will have injections for 6 or 7 days, normal volunteers for 5. A small blood sample will be drawn each day of the injections to monitor white cell counts and changes in the number of blood cell precursors. (Smaller children and all children under 10 years of age may have blood drawn on alternate days or less to reduce the number of needle sticks and the amount of blood taken.). Larger blood draws will be taken on days 6 and/or 7 for patients and on days 5 and/or 6 for normal volunteers.

- Leukapheresis This procedure for collecting larger numbers of circulating blood precursor cells is optional and may take the place of the larger blood draw described above. Patients 5 years old or older may have leukapheresis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The desired cells are then removed and the rest of the blood is returned to the body, either through the same needle or through a second one placed in the other arm. The cells obtained will be used to purify blood precursors for growing in culture and to examine the ability to transfer new genes into these precursor cells. For patients whose arm veins are too scarred to for needle placement, a vein in the groin area (femoral vein) may be used instead.

- Bone marrow aspiration This procedure for obtaining a bone marrow sample is optional. Normal volunteers who agree to the procedure may undergo aspiration up to three times. The hip area is anesthetized and a small sample of bone marrow is drawn through a special needle inserted in the hipbone. The first aspiration is done on a day before the G-CSF injections are started; the second is done soon after the last injection (day 6 or 7), and the third is done from 7 to 10 days after the last injection.

- Repeat blood tests At day 6 or 7 some of the blood tests done at the beginning of the study will be repeated to check blood counts and liver and kidney function.

Four months or more after the end of the study, participants will be asked to repeat the entire procedure to examine the effects of two cycles of G-CSF mobilization in the same individual. This second cycle is optional.

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Eligibility

ELIGIBILITY CRITERIA:

Healthy Volunteers:

1. Healthy adults aged 18-65 without active current infection or history of recurrent infection,

2. Weighs at least 50kg.

3. Normal renal function (creatinine less than or equal to 1.5 mg/dL; less than or equal to 1+ proteinuria); normal hepatic function (bilirubin less than or equal to 1.5 mg/dL); normal hematologic function (WBC greater than or equal to 2500/mm(3); granulocytes greater than or equal to 1200/mm(3); platelets greater than or equal to 120,000; hematocrit greater than or equal to 38).

4. Normal female volunteers of childbearing potential may be entered if using effective contraception and having a negative serum pregnancy test within one week of beginning G-CSF administration.

5. Willingness to allow blood cell samples to be stored

6. Willingness to allow blood and/or bone marrow samples to be modified to iPS cells

Patients (Patients with a genetically defined PID or clinical history consistent with PID):

1. Patients will have a genetically defined PID or have a clinical history of recurrent infections or other problems suggestive of PID, must be 2-70 years of age,

2. Is at least 10 kilograms body weight.

3. Some patients may have active bacterial or fungal infection at the time of study entry.

4. Preserved renal function (creatinine less than or equal to 2.5 mg/dL; less than or equal to 3+ proteinuria); preserved hepatic function (bilirubin less than or equal to 2.0 mg/dl); preserved hematologic function (WBC greater than or equal to 1000/mm(3); granulocytes greater than or equal to 500/mm(3); platelets greater than or equal to 100,000; hematocrit greater than or equal to 25). For those patients with chronic thrombocytopenia for which the collection is intended for clinical treatment (gene therapy or as rescue stem cells in the context of allogeneic stem cell transplant), patients may participate regardless of platelet count, but must have a platelet count > 40,000 on the day of first apheresis following any required platelet transfusion needed to achieve that level.

5. Patients of childbearing potential may be entered if using effective contraception and having a negative serum pregnancy test within one week of beginning G-CSF administration.

6.Patients may remain on their regimen of prophylactic treatments as deemed necessary by the investigator.

7. Willingness to allow blood cell samples to be stored

8. Willingness to allow blood and/or bone marrow samples to be modified to iPS cells

Healthy Donors (HLA matched sibling or other related donor of a patient with PID in need of an allogeneic hematopoietic stem cell transplant):

1. Healthy sibling or other relative of a patient with PID in need of an allogeneic transplant, between 2-65 years of age,

2. Is fully or closely HLA tissue matched to the patient with PID that the hematopoietic stem cell PBSC or bone marrow collection is designated to clinically benefit,

3. Is at least 10 kilograms body weight.

4. Normal renal function (creatinine less than or equal to 1.5 mg/dL; less than or equal to 1+ proteinuria); normal hepatic function (bilirubin less than or equal to 1.5 mg/dL); normal hematologic function (WBC greater than or equal to 2500/mm(3); granulocytes greater than or equal to 1200/mm(3); platelets greater than or equal to 120,000; hematocrit greater than or equal to 38).

5. Normal female donors of childbearing potential may be entered if using effective contraception and having a negative serum pregnancy test within one week of beginning G-CSF administration.

6. Willingness to allow blood cell samples to be stored

7. Willingness to allow blood and/or bone marrow samples to be modified to iPS cells

EXCLUSIONS:

Healthy Volunteers and Healthy Donors:

1. Active bacterial, fungal or viral infection as evidenced by history, physical exam (temperature > 38 degrees C), or WBC > 9000 are excluded.

2. Females who are pregnant or lactating as determined by history and/or pregnancy test are excluded.

3. History of vasculitis or similar disorder.

4. Must be negative by routine blood donor eligibility testing criteria including tests for syphilis (RPR) and TTV Recipient Transplant Panel (list is modified periodically, but may include hepatitis B and C, HIV and HTLV, T. cruzi) (These are routine tests for blood bank donors.)

5. Someone without peripheral venous access in arm veins adequate for apheresis.

6. If in the opinion of the investigator participation in this study places the healthy volunteer or donor at undue risk.

Patients:

1. Patients who are hemodynamically unstable (systolic or diastolic blood pressure fall of 20 mm Hg from the stable patient s baseline measurement) or requiring mechanical respiratory assistance are excluded.

2. Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test are excluded.

3. History of vasculitis or similar disorder.

4. Must be negative by routine blood donor eligibility testing criteria including tests for syphilis (RPR) and TTV Donor Transplant Panel testing (list is modified periodically, but may include hepatitis B and C, HIV and HTLV, T. cruzi).

--XSCID patients do not make antibodies and false positives may occur because they receive periodic infusions of pooled donations of IVIG. We have observed positive anti-HBc testing in these patients. If this occurs, more specific DNA or antigen testing will be done and must be negative.

--Autologous HSC Transplant patients may be positive for Hepatitis B and C if the investigator deems it necessary to be collected and used as a safety back-up graft.

Patients or Healthy Donors being considered for clinical scale bone marrow harvesting:

1. Who are unable to lie prone during the bone marrow harvesting procedure.

2. Who are unable to tolerate general anesthesia during the bone marrow harvesting procedure.


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Citations:

Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase-deficient severe combined immunodeficiency disease patients

Recominant human stem cell factor enhances myeloid colony growth from human peripheral blood progenitors

Single dose of filgrastim (rhG-CSF) increases the number of hematopoietic progenitors in the peripheral blood of adult volunteers

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Contacts:

Principal Investigator

Referral Contact

For more information:

Harry L. Malech, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10-CRC RM 5-3750
10 CENTER DR
BETHESDA MD 20814
(301) 480-6916
hmalech@nih.gov

Patricia L. Littel, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 6-3750
10 Center Drive
Bethesda, Maryland 20892
(301) 402-5964
plittel@cc.nih.gov

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

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT00001405

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