Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care Active Not specified NHLBI 557 U01 HL072305-01, HL072268, HL072291, HL072196, HL072248, HL072191, HL072305, HL072028, HL072072, HL072355, HL072283, HL072346, HL072331, HL072290, NCT00627393

Trial Description

Summary

Neutropenia, a condition characterized by an abnormally low number of infection-fighting white blood cells called neutrophils, commonly develops in people who have undergone chemotherapy or hematopoietic stem cell (HSC) transplantation. The severely reduced immunity of those with neutropenia can put them at risk of entry of life-threatening infections, making the implementation of treatments that increase white blood cell numbers important. Several studies have shown that the transfusion of donor granulocytes, a type of white blood cell that includes neutrophils, is effective in promoting the recovery of adequate numbers of granulocytes. However, granulocyte transfusions can cause side effects, and it is not known whether the success of the therapy outweighs the health risks of the side effects. This study will evaluate the safety and effectiveness of granulocyte transfusions in treating people with a bacterial or fungal infection during neutropenia.

Further Study Information

Thousands of people each year are hospitalized for neutropenia, which continues to cause substantial morbidity and mortality for those affected. Neutropenia is primarily caused by chemotherapy and various other cancer treatments, such as radiation therapy, biotherapy, and HSC transplantation. Signs and symptoms of neutropenia may include high fever, chills, sore throat, and diarrhea. In neutropenia, the number of neutrophils, a type of granulocyte, is greatly reduced, weakening the body's immune system and increasing the risk of infection. Therefore, a method to provide adequate numbers of functional granulocytes to people with neutropenia could be of greatest benefit for recovery. Administration of a combination of two drugs, granulocyte colony-stimulating factor (G-CSF) and dexamethasone, has been show to stimulate the body to produce a large number of granulocytes. Granulocyte transfusions obtained from donors who have received these two drugs may help people with low white blood cell counts fight infections until their own white blood cell counts recover. However, it is not clear whether the benefits of granulocyte transfusions outweigh the risks of side effects. This study will compare the safety and effectiveness of granulocyte transfusions with standard antimicrobial therapy versus the safety and effectiveness of standard antimicrobial therapy alone in increasing granulocyte numbers and in improving survival rates in people with bacterial or fungal infection during neutropenia.

Participation in the research portion of this study will last about 3 months. All participants who were not previously receiving treatment with standard antimicrobial therapy will begin therapy immediately upon study entry. Participants will then be assigned randomly to receive either granulocyte transfusion plus continued antimicrobial therapy or continued antimicrobial therapy alone. All participants will be monitored for a maximum of 42 days, during which they will provide information on medical history and ongoing status of antimicrobial therapy. Daily blood samples to measure white blood cell count will be obtained from participants until samples show that participants are making their own granulocytes. Samples will then be collected weekly until Day 42. There may be additional blood draws depending on the type of infection present in participants.

Granulocyte transfusions will be given daily during the 42-day treatment period, depending on granulocyte donor availability. Blood counts will be checked immediately before and after each transfusion to measure granulocyte levels. Transfusions will be stopped if participants start making their own granulocytes, experience serious side effects, or show a reduction in infection. At Month 3 after study entry, follow-up information will be collected about all participants' health status through reviewing their medical records and contacting their physicians.

Participation for granulocyte donors will last 1 week from the time of donation. Participants may provide more than one granulocyte donation, but no more than one donation every 3 days and eight donations each year. Twelve hours before each donation, participants will be injected with Neupogen, which contains G-CSF, and they will take one dose of dexamethasone by mouth. Participants will then undergo a blood draw, followed by a procedure using an apheresis machine for granulocyte collection. The procedure will last 3 to 4 hours and will involve the drawing of blood from each arm, the separation of granulocytes from the red blood cells and plasma in the machine, and the return of the red blood cells and plasma to the participants.

Eligibility Criteria

Inclusion Criteria:

• Undergone dose-intensive chemotherapy or HSC transplantation within 60 days before study entry

• Diagnosis of neutropenia (absolute neutrophil count less than 500 cells/mm3) and is expected to remain neutropenic for at least 5 days after study entry

• Must have one of the following: fungemia, bacteremia, invasive tissue bacterial infection, proven invasive tissue fungal infection, or probable invasive tissue fungal infection (Note: patients with criteria meeting only the definition for a possible invasive fungal infection are not eligible to participate)

Exclusion Criteria:

• Unlikely to survive 5 days

• Previously enrolled in this study

Trial Contact Information

Trial Lead Organizations/Sponsors

National Heart, Lung, and Blood Institute

Susan F. Assmann, PhD

Principal Investigator

Jan McFarland, MD

Principal Investigator

Eliot C. Williams

Principal Investigator

Ellis Neufeld, MD

Principal Investigator

James B. Bussel

Principal Investigator

Christopher Hillyer, MD

Principal Investigator

Paul M. Ness

Principal Investigator

Sherrill Slichter

Principal Investigator

Thomas Price, MD

Study Chair

Ronald Strauss, MD

Principal Investigator

Jeffrey McCullough, MD

Principal Investigator

Mark Brecher, MD

Principal Investigator

James George, MD

Principal Investigator

Barbara Konkle, MD

Principal Investigator

Catherine Manno, MD

Principal Investigator

Darrell Triulzi, MD

Principal Investigator

Susan F. Assmann, PhD		Ph: 617-923-7747 Ext.548
		Email: sassmann@neriscience.com

Julie Miller		Ph: 617-923-7747 Ext.497
		Email: jmiller@neriscience.com

U.S.A.
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Mark Reding, MD	Ph: 612-624-0123
			Email: redin002@umn.edu
		Jeffrey McCullough, MD	Principal Investigator
		Mark Reding, MD	Sub-Investigator
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Jennifer Holter, MD	Ph: 405-271-4222
			Email: jennifer-holter@ouhsc.edu
		James George, MD	Principal Investigator
		Jennifer Holter, MD	Sub-Investigator
Wisconsin
	Madison
	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
		Eliot Williams, MD	Ph: 608-262-5327
			Email: williams@medicine.wisc.edu
		Eliot C. Williams	Principal Investigator
	Milwaukee
	Froedtert Hospital and Medical College of Wisconsin
		Michael Lankiewicz, MD	Ph: 414-937-6416
			Email: michael.lankiewicz@bcw.edu
		Jan McFarland, MD	Principal Investigator
		Michael Lankiewicz, MD	Sub-Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00627393
Information obtained from ClinicalTrials.gov on September 15, 2008