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

NCT ID: NCT00001405

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 850 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1994-02-27

Brief Summary

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.

Detailed Description

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.

Participants include: 1. Adult patients with any primary immune deficiency (PID) or other blood disorder where collection is both for clinical use in another approved treatment protocol to benefit the patient and for laboratory research; 2. Adult patients with any primary immune deficiency (PID) or blood disorder where collection is for laboratory research use only. 3. Healthy adult volunteers where the collection is for laboratory research use only.

The majority of subjects will have HSC collected from peripheral blood by apheresis. Daily subcutaneous injections of G-CSF (granulocyte colony stimulating factor/filgrastim) for 5 to 6 days is a standard of care method used to mobilize HSC to the peripheral blood prior to apheresis, and will be used for most subjects. Plerixafor (Mozobil) is approved as standard of care for use in combination with G-CSF to mobilize HSC.

Some adult patients will have a clinical scale aspiration collection of bone marrow to obtain HSC for clinical use in another approved treatment protocol. Some adult participants may have a small sample needle aspiration collection of bone marrow obtained for laboratory research purposes only.

Mononuclear cells and/or Granulocytes (gran) will be collected from peripheral blood by apheresis following no stimulation, using G-CSF alone, or a using a combined single dose of G-CSF (480mcg) and Dexamethasone (8mg) prior to collection as is the standard of care pre-treatment used in the NIH DTM for collection of granulocyte transfusions from healthy donors.

As noted, HSC, mononuclear cells, and gran collection from patients with PID or other blood disorders may be used for laboratory research or may be designated for future clinical treatment of the patient under separate treatment protocol. HSC, mononuclear cells, and gran collection from healthy volunteers will be designated entirely for laboratory research.

HSC will be used for the following clinical purposes, where clinical treatments would occur under separate IRB approved protocols: 1. Autologous HSC from patients may be genetically modified and infused into the patient for treatment of an infection or the underlying disease (Gene therapy); 2. Autologous HSC from patients may serve as back up (rescue product) for patients undergoing matched unrelated donor transplantation or haploidential related or unrelated donor transplantation.

Mononuclear Cells (lymphocytes and monocytes) and granulocytes will be used for the following clinical purposes, 1. Autologous lymphocytes may be genetically modified and infused into the patient for treatment of an infection or the underlying disease (Gene therapy); 2. Autologous lymphocytes, monocytes and granulocytes (neutrophils) may be transfected with mRNAs to transiently express a therapeutic protein for treatment of an infection or the underlying disease (Gene therapy).

HSC, lymphocytes, monocytes and granulocytes will be used for laboratory research studies that include: Delineating the pathophysiology of inherited immune deficiencies; Delineating the physiology of and improving engraftment of hematopoietic stem cells; Determining how hematopoietic stem cells may be maintained in ex vivo culture without losing pluripotent potential; Delineating the molecular mechanisms responsible for lineage specific differentiation; Developing efficient methods for gene transfer into hematopoietic stem cells for corrective gene therapy; Developing methods for restoration of function in defective peripheral blood monocytes and/or granulocytes; Further characterization of peripheral blood monocytes and/or granulocytes from patients with PID.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Patients

Pts with PID or other blood disorder or clinical history consistent with PID or other blood disorder. Pts are able to volunteer as patient for research collection only per PI discretion.

No interventions assigned to this group

Healthy Volunteers

Healthy Adult Volunteers

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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.

1. 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.

2. 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.

3. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harry L Malech, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Joanna L Peterson

Role: CONTACT

joanna.peterson@nih.gov

(301) 346-9780

Harry L Malech, M.D.

Role: CONTACT

hmalech@nih.gov

(301) 480-6916

Facility Contacts

NIH Clinical Center Office of Patient Recruitment (OPR)

Role: primary

ccopr@nih.gov

800-411-1222 ext. TTY dial 711

Joanna Peterson

Role: backup

joanna.peterson@nih.gov

(301) 346-9780

References

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.

Reference Type: BACKGROUND

PMID: 8704221 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7517218 (View on PubMed)

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. doi: 10.1073/pnas.94.22.12133.

Reference Type: BACKGROUND

PMID: 9342375 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_1994-I-0073.html

NIH Clinical Center Detailed Web Page

Other Identifiers

94-I-0073

Identifier Type: -

Identifier Source: secondary_id

940073

Identifier Type: -

Identifier Source: org_study_id