Analysis of T Cell and Natural Killer (NK) Cell in Relation to Viral Infections in Pediatric Stem Cell Transplant Patients and Donors

Hematologic Malignancies Clinical Trial

Official title:

Analysis of KIR+CD56+ T Cells and FcRg-CD56+CD3- NK Cells in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients and Donors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02301065
• Other study ID #: KIRT
• Status: Completed
• Phase: N/A
• First received: November 18, 2014
• Last updated: July 14, 2017
• Start date: October 13, 2016
• Est. completion date: February 6, 2017

Study information

• Verified date: July 2017
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Viral infections and reactivation during pediatric allogeneic hematopoietic stem cell transplantation (HSCT) are a common occurrence and significantly contribute to post-transplant morbidity and mortality. The risk is high due to prolonged periods of immune deficiency while awaiting immune reconstitution post-transplant. Current strategies to reduce complications from viral infections include prophylactic treatment, close monitoring for viral infections and prompt treatment at the first sign of symptoms or increasing viral load. However, the most definitive treatment for viral infections remains the host's cellular defenses. Improved understanding of the immune systems response to viral infections may lead to better treatment strategies.

This study is being done to explore the relationships between T-cells and NK cells (infection fighting cells) and viral infections or reactivations in young allogeneic stem cell transplant patients. The investigators will be looking at how these cells react and function in young patients receiving allogeneic stem cell transplantation, as well as in healthy stem cell donors.

Description:

PRIMARY OBJECTIVE:

• To explore the expansion patterns of KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in response to viral infection and reactivation in pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients.

SECONDARY OBJECTIVES:

• To describe the phenotype of KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in pediatric allogeneic HSCT patients and healthy donors.

• To describe the specificity and functional capacity of KIR+CD56+ T-cells against viral antigens in both pediatric allogeneic HSCT patients and healthy donors.

• To describe the functional capacity of FcRg-CD56+CD3- NK cells against CMV-infected cells in both pediatric allogeneic HSCT patients and healthy donors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: February 6, 2017
• Est. primary completion date: February 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for a hematologic malignancy or a donor for a patient undergoing allogeneic hematopoietic stem cell transplant for a hematologic malignancy.

• For HSCT patients: ages birth to 21 years old; for donors: any age.

• For minors less than 18 years old, both parents must be available on St. Jude campus to provide consent. One parent/legal guardian will be acceptable if one parent is deceased, incompetent, or when the one parent present has legal responsibility for the care and custody of the child.

Exclusion Criteria:

• Patients undergoing allogeneic hematopoietic stem cell transplant for a disease other than a hematologic malignancy

Related Conditions & MeSH terms

• Hematologic Malignancies

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	Michigan State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of KIR+CD45+ T-cells in stem cell recipients and donors	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples: a baseline sample within 1 week prior to stem cell infusion and collections every 2 weeks, up to 100 days post-transplantation; Summary statistics of the two cell populations, such as mean, median, range, and standard error, will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 2 weeks, up to 100 days post-transplantation
Primary	Number of FcRg-CD56+CD3- NK cells in stem cell recipients and donors	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples: a baseline sample within 1 week prior to stem cell infusion and collections every 2 weeks, up to 100 days post-transplantation; Summary statistics of the two cell populations, such as mean, median, range, and standard error, will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 2 weeks, up to 100 days post-transplantation
Secondary	Surface marker expression density of phenotype KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in donors and recipients	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have two blood samples drawn: the first within 1 week prior to stem cell infusion, and the second within 1 week of 100 days post-transplantation; Surface marker expression density will be calculated and summary statistics will be provided for all calculations.	Donors once within 1 week prior to stem cell donation. HSCT recipients: within 1 week prior to stem cell infusion and within 1 week of 100 days post-transplantation
Secondary	Percentage of KIR+CD56+ T-cells that stain for tetramer/pentamer	Blood samples will be drawn as follows: Donors will have percentages measured once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples, a baseline sample within 1 week prior to stem cell infusion, and collections every 28 days, up to 100 days post-transplantation; The specificity of KIR+CD56+T-cells will be evaluated through viral tetramer/pentamer staining.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 28 days, up to 100 days post-transplantation
Secondary	Change in numbers and percentages of KIR+CD56+T-cells after exposure to viral antigen in vitro and cytokine expression levels	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples, including a baseline sample within 1 week prior to stem cell infusion and collections every 28 days, up to 100 days post-transplantation; The functional capacity of KIR+CD56+T-cells will be evaluated through proliferation and cytokine production assays. Summary statistics will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 28 days, up to 100 days post-transplantation
Secondary	Number of FcRg-CD56+CD3- NK cells after exposure to cytomegalovirus	Blood samples will be drawn as follows: Donors will have will have one blood sample drawn within 1 week prior to stem cell donation.; HSCT recipients will have two blood samples drawn: the first within 1 week prior to stem cell infusion, and the second within 1 week of 100 days post-transplantation; Summary statistics of the functional capacity of FcRg-CD56+CD3- NK against CMV-infected cells will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: within 1 week prior to stem cell infusion and within 1 week of 100 days post-transplantation

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital