Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)

NCT ID: NCT00627393

Last Updated: 2015-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2013-05-31

Brief 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.

Detailed Description

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. Community donors may provide more than one granulocyte donation, but no more than one donation every 3 days. Frequency of donation from a family member will be according to local blood bank criteria with approval from a blood bank physician. Both community donors and family donors are limited to 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.

Conditions

Neutropenia; Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1

Participants will receive granulocyte transfusions in addition to standard antimicrobial therapy

Group Type: EXPERIMENTAL

Standard antimicrobial therapy

Intervention Type: DRUG

Antimicrobial therapy is broadly defined as therapy within the standard of care for a particular infection and should be consistent within a given institution. Participants will undergo the recommended therapy for specific infections for 42 days.

Granulocyte transfusions

Intervention Type: BIOLOGICAL

Participants will receive one granulocyte transfusion per day until one of the following occurs: recovery from neutropenia, life-threatening toxicity, resolution or improvement of infection, or Day 42 after treatment. Granulocyte content of each transfusion is targeted to be at least 4 x 10\^10 per collection (or proportionately less for participants less than 30 kg in weight).

2

Participants will receive standard antimicrobial therapy alone

Group Type: ACTIVE_COMPARATOR

Standard antimicrobial therapy

Intervention Type: DRUG

Antimicrobial therapy is broadly defined as therapy within the standard of care for a particular infection and should be consistent within a given institution. Participants will undergo the recommended therapy for specific infections for 42 days.

3

Participants will donate granulocytes after receiving a combination of two drugs, G-CSF and dexamethasone

Group Type: OTHER

G-CSF/dexamethasone

Intervention Type: DRUG

Twelve hours before each donation, participants will be injected with G-CSF and will take one dose of dexamethasone by mouth.

Apheresis machine

Intervention Type: DEVICE

Participants will undergo 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 cells and plasma in the machine, and the return of the red cells and plasma to the participants.

Interventions

Standard antimicrobial therapy

Antimicrobial therapy is broadly defined as therapy within the standard of care for a particular infection and should be consistent within a given institution. Participants will undergo the recommended therapy for specific infections for 42 days.

Intervention Type: DRUG

Granulocyte transfusions

Participants will receive one granulocyte transfusion per day until one of the following occurs: recovery from neutropenia, life-threatening toxicity, resolution or improvement of infection, or Day 42 after treatment. Granulocyte content of each transfusion is targeted to be at least 4 x 10\^10 per collection (or proportionately less for participants less than 30 kg in weight).

Intervention Type: BIOLOGICAL

G-CSF/dexamethasone

Twelve hours before each donation, participants will be injected with G-CSF and will take one dose of dexamethasone by mouth.

Intervention Type: DRUG

Apheresis machine

Participants will undergo 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 cells and plasma in the machine, and the return of the red cells and plasma to the participants.

Intervention Type: DEVICE

Other Intervention Names

Neupogen

Eligibility Criteria

Inclusion Criteria

• Severe neutropenia (Absolute Neutrophil Count < 500/mm^3) due to marrow failure caused by underlying disease or therapy
• Must have one of the following: fungemia; bacteremia; proven or presumptive invasive tissue bacterial infection; or proven, probable, or presumptive invasive fungal infection

Exclusion Criteria

• Unlikely to survive 5 days
• Evidence that patient will not be neutropenic at least 5 days
• Previously enrolled in this study

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Carelon Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan F. Assmann, PhD

Role: PRINCIPAL_INVESTIGATOR

Carelon Research

Jan McFarland, MD

Role: PRINCIPAL_INVESTIGATOR

Froedtert Hospital

Eliot Williams, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Ellis Neufeld, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Boston/Brigham and Women's Hospital

James Bussel, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College, Cornell University

Cassandra Josephson, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Paul Ness, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Sherrill Slichter, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Thomas Price, MD

Role: STUDY_CHAIR

Bloodworks

Ronald Strauss, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Jeffrey McCullough, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

James George, MD

Role: PRINCIPAL_INVESTIGATOR

University of Oklahoma

Bruce Sachais, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

David Friedman, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Darrell Triulzi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Presbyterian and Shadyside/Children's Hospital Pittsburgh

Locations

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Children's Hospital Boston

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Weill Medical College, Cornell University

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Chlidren's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Presbyterian and Shadyside

Pittsburgh, Pennsylvania, United States

University of Washington Medical Center

Seattle, Washington, United States

University of Wisconsin at Madison

Madison, Wisconsin, United States

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Countries

United States

References

Price TH, Boeckh M, Harrison RW, McCullough J, Ness PM, Strauss RG, Nichols WG, Hamza TH, Cushing MM, King KE, Young JA, Williams E, McFarland J, Holter Chakrabarty J, Sloan SR, Friedman D, Parekh S, Sachais BS, Kiss JE, Assmann SF. Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection. Blood. 2015 Oct 29;126(18):2153-61. doi: 10.1182/blood-2015-05-645986. Epub 2015 Sep 2.

Reference Type: DERIVED

PMID: 26333778 (View on PubMed)

Other Identifiers

U01HL072268

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HL072268

Identifier Type: -

Identifier Source: secondary_id

HL072291

Identifier Type: -

Identifier Source: secondary_id

HL072196

Identifier Type: -

Identifier Source: secondary_id

HL072248

Identifier Type: -

Identifier Source: secondary_id

HL072191

Identifier Type: -

Identifier Source: secondary_id

HL072305

Identifier Type: -

Identifier Source: secondary_id

HL072028

Identifier Type: -

Identifier Source: secondary_id

HL072072

Identifier Type: -

Identifier Source: secondary_id

HL072355

Identifier Type: -

Identifier Source: secondary_id

HL072283

Identifier Type: -

Identifier Source: secondary_id

HL072346

Identifier Type: -

Identifier Source: secondary_id

HL072331

Identifier Type: -

Identifier Source: secondary_id

HL072290

Identifier Type: -

Identifier Source: secondary_id

557

Identifier Type: -

Identifier Source: org_study_id