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Protocol Details

Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells, Mononuclear Cells and Granulocytes

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: 18 Years
Max Age: 70 Years

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

Chronic Granulomatous Disease;
CD34 Cells;
Infection;
Nadph Oxidase;
Healthy Volunteer;
Natural History

Recruitment Keyword(s)

Normal Volunteer

Condition(s)

Granuloma;
Granulomatous Disease, Chronic;
Leukocyte Disease;
Genetic Disease, X-Linked;
Genetic Disease, Inborn

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Allergy and Infectious Diseases

The research goal of this study is to obtain CD34+ hematopoietic stem cells (HSC) from peripheral blood and/or bone marrow, and Mononuclear Cells (lymphocytes and monocytes), and granulocytes (grans) from peripheral blood that will be used in the laboratory and/or in the clinic to develop new cell therapies for patients with inherited or acquired disorders of immunity or blood cells. Development of novel cellular therapies requires access to HSC, Mononuclear Cells and/or granulocytes as the essential starting materials for the pre-clinical laboratory development of gene therapies and other engineered cell products. HSC or blood cells from healthy adult volunteers serve both as necessary experimental controls and also as surrogates for patient cells for clinical scale-up development. HSC or blood cells from patients serve both as the necessary experimental substrate for novel gene therapy and cellular engineering development for specific disorders and as pre-clinical scale up of cellular therapies. Collection of cells from adult patients collected in the NIH Department of Transfusion Medicine (DTM) under conditions conforming to accepted blood banking clinical practice may also be used directly in or cryopreserved for future use in other NIH protocols that have all required regulatory approvals allowing such use. In summary, the research goal of this protocol is the collection of HSC or blood cells that may be used for both laboratory research and/or for clinical treatment in other approved protocols.

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Eligibility

ELIGIBILITY CRITERIA:

Patients (Patients with a genetically defined PID or other blood disorder or clinical history consistent with PID or other blood disorder)

1. Patients will have a genetically defined PID or have a clinical history of recurrent infections or other problems suggestive of PID or other blood disorder, must be 18-70 years of age,

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

3. 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 to1000/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). Of note, patients with PID often have associated chronic thrombocytopenia. Patients with stable chronic thrombocytopenia will be eligible for collection, at the investigator s discretion, with the caveat that patients with platelet count <40,000 the day prior to collection will be transfused with platelets on the morning of collection. Platelets may also be given to these patients following the collection if medically indicated..

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

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

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

Healthy Adult 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 or urine pregnancy test within one week of beginning GCSF 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

For PBMCs and grans collections, adult subjects with known genetic mutations may participate as healthy volunteers for research purposes as long as the other criteria listed above are fulfilled.

EXCLUSIONS:

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. 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). This does not apply to leukapheresis patients, as these tests are not required by DTM.

a. 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.

b. Patients with CGD and other patients with autoimmunity as part of their PID phenotype may have false positive antibody tests and if this occurs more specific DNA or antigen testing will be done and must be negative.

c. 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

Healthy Volunteers

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

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

3. 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) This does not apply to leukaphersis patients, as these tests are not required by DTM policy.

4. Someone without peripheral venous access in arm veins adequate for apheresis (healthy volunteers only).

5. If in the opinion of the investigator participation in this study places the healthy adult volunteer at undue risk.

Patients 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:

Sekhsaria S, Fleisher TA, Vowells S, Brown M, Miller J, Gordon I, Blaese RM, Dunbar CE, Leitman S, Malech HL. 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. Blood. 1996 Aug 1;88(3):1104-12. PMID: 8704221.

Li F, Linton GF, Sekhsaria S, Whiting-Theobald N, Katkin JP, Gallin JI, Malech HL. CD34+ peripheral blood progenitors as a target for genetic correction of the two flavocytochrome b558 defective forms of chronic granulomatous disease. Blood. 1994 Jul 1;84(1):53-8.

Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S, Vowells SJ, Li F, Miller JA, DeCarlo E, Holland SM, Leitman SF, Carter CS, Butz RE, Read EJ, Fleisher TA, Schneiderman RD, Van Epps DE, Spratt SK, Maack CA, Rokovich JA, Cohen LK, Gallin JI. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12133-8.

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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)
NIHBC 10 - CRC BG RM 5-3750
10 CENTER DR
BETHESDA MD 20892
(301) 480-6916
hmalech@nih.gov

Joanna L. Peterson
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 13N254
10 Center Drive
Bethesda, Maryland 20892
(240) 292-4291
joanna.peterson@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT00001405

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