Improving White Blood Cell Collection From Healthy Donors

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ClinicalTrials.gov Identifier: NCT01553214

Recruitment Status : Recruiting

First Posted : March 14, 2012

Last Update Posted : October 31, 2018

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Sponsor:

Information provided by:

National Institutes of Health Clinical Center (CC)

Study Description

Brief Summary:

Background:

- White blood cells called granulocytes help the body fight infection. People who have had chemotherapy or bone marrow transplants may have very low numbers of these cells. Transfusions of these cells can help improve the body's ability to fight infection. However, most of the cells are located in the bone marrow or spleen, and are hard to collect from healthy donors. Two drugs, filgrastim and dexamethasone, can help move the cells to the bloodstream to be collected by apheresis. Researchers want to study the best ways to collect these white blood cells. They also want to monitor the effects of the injections and donations on the volunteer donors.

Objectives:

- To improve the amount and quality of granulocytes (white blood cells) collected by apheresis for donation.

Eligibility:

- Healthy volunteers between 18 and 75 years of age.

Design:

Participants will be screened with a physical exam and medical history. Initial blood tests will be done to check for eligibility.
Participants will donate granulocytes by apheresis a maximum of 12 times in 1 year. Donations will not usually be requested more often than every 4 weeks. Donors will be allowed to decline participation at any time.
Participants will have one injection of filgrastim 12 to 24 hours before donation. They will also have two tablets of dexamethasone 12 hours before donation.
White blood cells will be collected through apheresis. The apheresis will last about 2 hours.
Participants will be eligible to donate until they reach their 76th birthday.

Condition or disease	Intervention/treatment	Phase
Blood Donor Leukocyte Transfusion Granulocyte Colony-Stimulation Factor Blood Component Removal	Drug: Filgrastim (G-CSF) Drug: Dexamethasone	Phase 1

Detailed Description:

Bacterial and fungal infections in neutropenic patients or in patients with inherited disorders of neutrophil function continue to cause substantial morbidity and mortality. In particular, fungal infections are an increasingly important cause of death in patients receiving aggressive chemotherapy, in patients undergoing hematopoietic stem cell transplantation (HSCT), in patients with chronic granulomatous disease, and in patients with bone marrow failure syndromes such as severe aplastic anemia. The strongest predictor of progression and death from invasive mold infection in the cancer/ HSCT setting is the duration of neutropenia. Any modality which increases the granulocyte count during periods of profound neutropenia and severe infection is thus likely to be of clinical benefit. In the 1970-80 s, collection of granulocyte concentrates by apheresis of healthy donors stimulated with corticosteroids alone yielded products with an insufficient number of granulocytes to substantially raise the circulating counts in neutropenic patients. Transfusion of such components was variably associated with clinical benefit. More recently, the ability to give donors recombinant human granulocyte colony-stimulating factor (G-CSF) in combination with corticosteroids (dexamethasone) dramatically increases the circulating neutrophil count prior to apheresis and results in the collection of granulocyte concentrates containing 2 to 6 times as many cells as those collected using steroids alone. Transfusion of granulocyte concentrates collected after G-CSF and dexamethasone stimulation of the donor typically increases the recipient s granulocyte count by 1,000 cells/uL, and the increase in counts is generally sustained for 24 to 48 hours. Transfusion of daily or every other day granulocytes derived by apheresis of G-CSF and dexamethasone-stimulated donors has been associated in observational and retrospective studies with clearance of life-threatening infections in neutropenic patients, but a single small randomized prospective study did not demonstrate improved survival in neutropenic infected patients who received granulocytes. Granulocyte components are not recognized as a licensed blood component by the Food and Drug Administration (FDA), and neither G-CSF nor dexamethasone is approved by the FDA for use in allogeneic granulocytapheresis donors. Studies at the NIH Department of Transfusion Medicine (DTM) have defined the optimal timing and dose of these drugs in granulocyte donors, and these components have been used for clinical care since 1996. Short term adverse effects of G-CSF and dexamethasone, including bone pain, myalgias, headache, insomnia and fatigue, are well known and possible long term effects, including cataracts from serial steroid administration, have been described. The purpose of the current protocol is to determine the operational feasibility of managing a volunteer community donor granulocytapheresis program and to provide informed consent for the administration of filgrastim and dexamethasone to volunteer donors donating granulocytes by apheresis. Donor accrual and retention, immediate short term adverse effects of G-CSF and dexamethasone, and any long term effects, will be assessed in healthy subjects who will be permitted to donate granulocytes a maximum of 12 times per year. Participants will be selected based on general blood donor eligibility criteria, adequacy of antecubital venous access, and interest in the program. Most subjects will already have experience as plateletpheresis donors. The toxicity of granulocyte transfusions and the survival and discharge rates of the transfusion recipients will be monitored, but the protocol is not designed to evaluate the efficacy of granulocyte transfusions.

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1000 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Other
Official Title:	Collection of Granulocytes by Apheresis of Healthy Donors Stimulated With Filgrastim (G-CSF) and Dexamethasone
Study Start Date :	March 7, 2012
Estimated Primary Completion Date :	January 1, 2032
Estimated Study Completion Date :	January 1, 2032

Resource links provided by the National Library of Medicine

Drug Information available for: Dexamethasone Dexamethasone sodium phosphate Dexamethasone acetate Filgrastim

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
1 There are no arms in this study	Drug: Filgrastim (G-CSF) Recombinant G-CSF is available from the Clinical Center pharmacy in colorless glass, single-use vials containing 480 mcg G-CSF in 1.6 mL vials (300 mcg/mL). It is formulated as a sterile, clear, colorless liquid in 10 mm sodium acetate buffer at pH 4.0. The quantitative composition (per mL) is: Recombinant human G-CSF 300 mcg Acetate 0.59 mg Mannitol 50 mg Tween 80TM 0.004% Sodium 0.035 mg Water for injection (qs ad) to 1.0 mL Storage: The intact vials of G-CSF should be stored under refrigeration (2-8 degrees Celsius). Administration: G-CSF is administered subcutaneously, with the entire contents of one 1.6 mL vial given in one injection 12 to 24 hours prior to apheresis.Stability: G-CSF in the intact vial is stable for 36 months when stored in a refrigerator at 2-8 degrees Celsius. A single brief exposure (up to 7 days) to elevated temperatures (<37 degrees Celsius) does not affect the stability. G-CSF should not be frozen, and vials that have been frozen should not be used. Drug: Dexamethasone Oral dexamethasone is available from the Clinical Center pharmacy as green 4 mg tablets. The tablets contain the following inactive ingredients: lactose monohydrate, magnesium stearate, starch, sucrose, FD&C Green No. 3, FD&C Yellow No. 10, and FD&C Yellow No. 6. They are packaged in unit-dose blister pack strips. Storage: Dexamethasone tablets should be stored at room temperature (20-25 degrees Celsius). Administration: Dexamethasone is administered as two 4-mg tablets 12 hours prior to apheresis (approximately one hour after dinner the evening prior to apheresis). Stability: Dexamethasone is stable for 36 months when stored at room temperature in an unopened blister pack.
2 There are no arms in this study	Drug: Filgrastim (G-CSF) Recombinant G-CSF is available from the Clinical Center pharmacy in colorless glass, single-use vials containing 480 mcg G-CSF in 1.6 mL vials (300 mcg/mL). It is formulated as a sterile, clear, colorless liquid in 10 mm sodium acetate buffer at pH 4.0. The quantitative composition (per mL) is: Recombinant human G-CSF 300 mcg Acetate 0.59 mg Mannitol 50 mg Tween 80TM 0.004% Sodium 0.035 mg Water for injection (qs ad) to 1.0 mL Storage: The intact vials of G-CSF should be stored under refrigeration (2-8 degrees Celsius). Administration: G-CSF is administered subcutaneously, with the entire contents of one 1.6 mL vial given in one injection 12 to 24 hours prior to apheresis.Stability: G-CSF in the intact vial is stable for 36 months when stored in a refrigerator at 2-8 degrees Celsius. A single brief exposure (up to 7 days) to elevated temperatures (<37 degrees Celsius) does not affect the stability. G-CSF should not be frozen, and vials that have been frozen should not be used. Drug: Dexamethasone Oral dexamethasone is available from the Clinical Center pharmacy as green 4 mg tablets. The tablets contain the following inactive ingredients: lactose monohydrate, magnesium stearate, starch, sucrose, FD&C Green No. 3, FD&C Yellow No. 10, and FD&C Yellow No. 6. They are packaged in unit-dose blister pack strips. Storage: Dexamethasone tablets should be stored at room temperature (20-25 degrees Celsius). Administration: Dexamethasone is administered as two 4-mg tablets 12 hours prior to apheresis (approximately one hour after dinner the evening prior to apheresis). Stability: Dexamethasone is stable for 36 months when stored at room temperature in an unopened blister pack.
3 There are no arms in this study	Drug: Filgrastim (G-CSF) Recombinant G-CSF is available from the Clinical Center pharmacy in colorless glass, single-use vials containing 480 mcg G-CSF in 1.6 mL vials (300 mcg/mL). It is formulated as a sterile, clear, colorless liquid in 10 mm sodium acetate buffer at pH 4.0. The quantitative composition (per mL) is: Recombinant human G-CSF 300 mcg Acetate 0.59 mg Mannitol 50 mg Tween 80TM 0.004% Sodium 0.035 mg Water for injection (qs ad) to 1.0 mL Storage: The intact vials of G-CSF should be stored under refrigeration (2-8 degrees Celsius). Administration: G-CSF is administered subcutaneously, with the entire contents of one 1.6 mL vial given in one injection 12 to 24 hours prior to apheresis.Stability: G-CSF in the intact vial is stable for 36 months when stored in a refrigerator at 2-8 degrees Celsius. A single brief exposure (up to 7 days) to elevated temperatures (<37 degrees Celsius) does not affect the stability. G-CSF should not be frozen, and vials that have been frozen should not be used.
4 There are no arms in this study	Drug: Filgrastim (G-CSF) Recombinant G-CSF is available from the Clinical Center pharmacy in colorless glass, single-use vials containing 480 mcg G-CSF in 1.6 mL vials (300 mcg/mL). It is formulated as a sterile, clear, colorless liquid in 10 mm sodium acetate buffer at pH 4.0. The quantitative composition (per mL) is: Recombinant human G-CSF 300 mcg Acetate 0.59 mg Mannitol 50 mg Tween 80TM 0.004% Sodium 0.035 mg Water for injection (qs ad) to 1.0 mL Storage: The intact vials of G-CSF should be stored under refrigeration (2-8 degrees Celsius). Administration: G-CSF is administered subcutaneously, with the entire contents of one 1.6 mL vial given in one injection 12 to 24 hours prior to apheresis.Stability: G-CSF in the intact vial is stable for 36 months when stored in a refrigerator at 2-8 degrees Celsius. A single brief exposure (up to 7 days) to elevated temperatures (<37 degrees Celsius) does not affect the stability. G-CSF should not be frozen, and vials that have been frozen should not be used.

Outcome Measures

Primary Outcome Measures :

To determine the operational feasibility and impact of managing a volunteer community donor granulocytapheresis program [ Time Frame: Annually. The feasibility of continuing the granulocyte donation program will be assessed, based on resource need and allocation, operational impact, adverse effects in donors, and survival outcomes of recipients. ]

Secondary Outcome Measures :

To monitor the frequency and severity (symptom grade) of acute adverse effects due to a single dose of filgrastim and dexamethasone in volunteer donors [ Time Frame: 48 hours after last GCSF dose. The feasibility of continuing the granulocyte donation program will be assessed, based on resource need and allocation, operational impact, adverse effects in donors, and survival outcomes of recipients. ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

INCLUSION CRITERIA:
Donors shall meet all donor eligibility criteria for allogeneic blood donors, as defined in the most recent editions of the AABB Standards and FDA Code of Federal Regulations (21CFR640). In addition, donors shall meet the following restrictions:
Age greater than or equal to18 and less than or equal to 75 years
If hypertension is present, must be well-controlled on medications
If peptic ulcer disease has been diagnosed in the past, symptoms must be well-controlled on medications
If cataracts have been diagnosed in the past, records from subject s ophthalmologist must be obtained indicating type of cataract. If PSC was diagnosed in the past, subject may receive G-CSF but not dexamethasone. The only exception to this is a history of bilateral cataract extractions due to PSC.

EXCLUSION CRITERIA:

Information obtained from health history screen that does not meet the allogeneic donor eligibility criteria of the AABB Standards or the FDA CFR.
Weight less than 50 kg (110 lbs)
History of coronary heart disease
Uncontrolled hypertension (systolic BP >160, diastolic BP >100)
History of hepatitis or injection drug use
Diabetes mellitus requiring insulin
Active, symptomatic peptic ulcer disease
History of iritis or episcleritis
Sickle cell disease (sickle trait is acceptable). Testing for hemoglobin S is not required.
Lithium therapy
Pregnancy or nursing (breast feeding)
Renal function eGFR < 45 ml/min/1.73m(2)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01553214

Contacts


Contact: Yu Ying Yau, R.N.	(301) 435-3049	yyau@mail.cc.nih.gov
Contact: Kathleen A Cantilena, M.D.	(301) 451-8637	ccantilena@mail.nih.gov

Locations


United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institutes of Health Clinical Center (CC)

Investigators


Principal Investigator:	Kathleen A Cantilena, M.D.	National Institutes of Health Clinical Center (CC)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, Baden LR, Gersten ID, Mendizabal AM, Leather HL, Confer DL, Maziarz RT, Stadtmauer EA, Bolaños-Meade J, Brown J, Dipersio JF, Boeckh M, Marr KA; Blood and Marrow Transplant Clinical Trials Network. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010 Dec 9;116(24):5111-8. doi: 10.1182/blood-2010-02-268151. Epub 2010 Sep 8.

Baddley JW, Andes DR, Marr KA, Kontoyiannis DP, Alexander BD, Kauffman CA, Oster RA, Anaissie EJ, Walsh TJ, Schuster MG, Wingard JR, Patterson TF, Ito JI, Williams OD, Chiller T, Pappas PG. Factors associated with mortality in transplant patients with invasive aspergillosis. Clin Infect Dis. 2010 Jun 15;50(12):1559-67. doi: 10.1086/652768.

Stroncek DF, Yau YY, Oblitas J, Leitman SF. Administration of G--CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more donor toxicity than G--CSF alone. Transfusion. 2001 Aug;41(8):1037-44.


ClinicalTrials.gov Identifier:	NCT01553214 History of Changes
Other Study ID Numbers:	120096 12-CC-0096
First Posted:	March 14, 2012 Key Record Dates
Last Update Posted:	October 31, 2018
Last Verified:	October 25, 2018


Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by National Institutes of Health Clinical Center (CC):


Healthy Volunteers Granulocyte Transfusion Granulocytapheresis Leukapheresis	Cytokine Stimulation Healthy Volunteer HV

Additional relevant MeSH terms:


Dexamethasone acetate Dexamethasone BB 1101 Lenograstim Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents	Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Adjuvants, Immunologic Immunologic Factors

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