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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00627393
First received: February 28, 2008
Last updated: April 16, 2014
Last verified: April 2014

February 28, 2008
April 16, 2014
April 2008
April 2013   (final data collection date for primary outcome measure)
Percentage of participants who are alive at 42 days after treatment and have had microbial response [ Time Frame: Measured at Day 42 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00627393 on ClinicalTrials.gov Archive Site
  • Alloimmunization, defined as the appearance of anti-human leukocyte antigen (HLA) or antineutrophil antibodies [ Time Frame: Measured at Days 14 and 42 ] [ Designated as safety issue: Yes ]
  • Serious granulocyte transfusion reactions, including febrile, allergic, and pulmonary reactions (transfusion arm only) [ Time Frame: Measured within 6 hours after end of transfusion ] [ Designated as safety issue: Yes ]
  • Graft versus host disease among recipients of allogeneic stem cell transplantation [ Time Frame: Measured at Day 42 ] [ Designated as safety issue: Yes ]
  • Overall incidence of adverse effects [ Time Frame: Measured through Day 42 ] [ Designated as safety issue: Yes ]
  • Time to resolve fever [ Time Frame: Measured through Day 42 ] [ Designated as safety issue: No ]
  • Time to negative test for fungal antigenemia (e.g., galactomannan antigenemia among participants with invasive aspergillosis) [ Time Frame: Measured at Days 7, 14, and 42 ] [ Designated as safety issue: No ]
  • Time to negative blood culture for participants with positive blood culture at baseline [ Time Frame: Measured through Day 42 ] [ Designated as safety issue: No ]
  • Long-term survival [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
  • Serious adverse events in granulocyte donors [ Time Frame: Measured at Week 1 after G-CSF administration ] [ Designated as safety issue: Yes ]
  • Donor availability (proportion of scheduled granulocyte transfusion days on which granulocytes were available) [ Time Frame: Measured through study completion ] [ Designated as safety issue: No ]
  • Evaluation of granulocyte yield [ Time Frame: Measured immediately after each granulocyte donation ] [ Designated as safety issue: No ]
  • Discontinuation of granulocyte transfusions due to toxicity or intolerance [ Time Frame: Measured through Day 42 ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
High Dose Granulocyte Transfusions for the Treatment of Infection in Neutropenia: The RING Study (Resolving Infection in Neutropenia With Granulocytes)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
  • Neutropenia
  • Infection
  • Drug: 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.
  • Biological: 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).
  • Drug: G-CFS/dexamethasone
    Twelve hours before each donation, participants will be injected with G-CSF and will take one dose of dexamethasone by mouth.
    Other Name: Neupogen
  • Device: 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.
  • Experimental: 1
    Participants will receive granulocyte transfusions in addition to standard antimicrobial therapy
    Interventions:
    • Drug: Standard antimicrobial therapy
    • Biological: Granulocyte transfusions
  • Active Comparator: 2
    Participants will receive standard antimicrobial therapy alone
    Intervention: Drug: Standard antimicrobial therapy
  • 3
    Participants will donate granulocytes after receiving a combination of two drugs, G-CSF and dexamethasone
    Interventions:
    • Drug: G-CFS/dexamethasone
    • Device: Apheresis machine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
114
May 2013
April 2013   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00627393
557, U01HL072268, HL072268, HL072291, HL072196, HL072248, HL072191, HL072305, HL072028, HL072072, HL072355, HL072283, HL072346, HL072331, HL072290
Yes
New England Research Institutes
New England Research Institutes
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Susan F. Assmann, PhD New England Research Institutes
Principal Investigator: Jan McFarland, MD Froedtert Memorial Lutheran Hospital
Principal Investigator: Eliot Williams, MD University of Wisconsin, Madison
Principal Investigator: Ellis Neufeld, MD Children's Hospital Boston/Brigham and Women's Hospital
Principal Investigator: James Bussel, MD Weill Medical College, Cornell University
Principal Investigator: Cassandra Josephson, MD Emory University
Principal Investigator: Paul Ness, MD Johns Hopkins University
Principal Investigator: Sherrill Slichter, MD University of Washington
Study Chair: Thomas Price, MD Puget Sound Blood Center
Principal Investigator: Ronald Strauss, MD University of Iowa
Principal Investigator: Jeffrey McCullough, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: James George, MD University of Oklahoma
Principal Investigator: Bruce Sachais, MD, PHD University of Pennsylvania
Principal Investigator: David Friedman, MD Children's Hospital of Philadelphia
Principal Investigator: Darrell Triulzi, MD University of Pittsburgh Presbyterian and Shadyside/Children's Hospital Pittsburgh
New England Research Institutes
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP