NCT03063242

Brief Summary

The study will determine whether administration of sargramostim will improve myeloid dendritic cell deficiency in various study groups, including healthy subjects and patients with chronic kidney disease, including those with kidney transplants.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2017

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 21, 2017

Completed
2 days until next milestone

Study Start

First participant enrolled

February 23, 2017

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 24, 2017

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 17, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 17, 2018

Completed
Last Updated

December 31, 2018

Status Verified

December 1, 2018

Enrollment Period

1.6 years

First QC Date

February 21, 2017

Last Update Submit

December 27, 2018

Conditions

Keywords

Sargramostim

Outcome Measures

Primary Outcomes (1)

  • Change in peripheral blood mDC levels

    mDC levels to \>2.0 x104 mDCs/mL, with the target level defined as levels at or above upper quartile values in healthy controls

    Baseline to 2 weeks

Secondary Outcomes (2)

  • Proportion of patients with adverse events during the intervention.

    Baseline to 2 weeks

  • Increase in T cell levels, mDC Interleukin (IL)-12 production, and interferon-gamma (IFN-y) production in QuantiFERON-CMV and QuantiFERON-Monitor assays after the intervention.

    Baseline to 2 weeks

Study Arms (3)

Project I: Healthy participants

EXPERIMENTAL

5 healthy participants will be used to optimize the dosage and timing of sargramostim administration with regard to the primary and secondary outcomes. Blood samples will be drawn and analyzed for mDC levels.

Drug: SargramostimBiological: Blood samples

Project II: Patients with CKD stage IV/V

EXPERIMENTAL

5 Patients with CKD stage IV/V who are cytomegalovirus (CMV) seropositive with mean blood mDC levels \<1.0x104/mL will receive sargramostim treatment once all 5 healthy participants have completed treatment and the data have been analyzed to guide subsequent dosing. Blood samples will be drawn and analyzed for mDC levels.

Drug: SargramostimBiological: Blood samples

Project III: kidney transplant patients

EXPERIMENTAL

5 Kidney transplant recipients who are CMV seropositive with neutropenia (defined as absolute neutrophil count \<1.0 x103/mm3) and/or CMV viremia will receive sargramostim treatment once all 5 Project I participants have completed treatment and the data have been analyzed to guide subsequent dosing. Blood samples will be drawn and analyzed for mDC levels.

Drug: SargramostimBiological: Blood samples

Interventions

Study participants (n=5 per project) will receive subcutaneous injection of sargramostim (6 ug/kg) daily until maximal mDC levels are achieved, as determined by a dose response curve.

Also known as: Leukine®, GM-CSF
Project I: Healthy participantsProject II: Patients with CKD stage IV/VProject III: kidney transplant patients
Blood samplesBIOLOGICAL

Blood samples will be drawn at baseline and during each subsequent visit

Project I: Healthy participantsProject II: Patients with CKD stage IV/VProject III: kidney transplant patients

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \>18 years \< 80 years
  • Absence of acute or chronic medical condition and taking no prescription medications (Project I)
  • Stable native or transplant kidney function (Project II/III)

You may not qualify if:

  • Age \< 18 or \> 80 years
  • History of non-adherence to prescribed medications (Projects II and III)
  • Active drug or heavy alcohol use (defined as \> 4 drinks/day)
  • Pregnancy or breast feeding
  • Active infection (bacterial or viral) or clinically significant infections within the past three months (e.g. those requiring hospitalization, or as judged by the PI, except for CMV viremia in Project III)
  • Active malignancy (with the exception of excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or adequately treated pre-invasive cervical cancer in situ)
  • Unstable cardiovascular status (angina, arrhythmias, congestive heart failure (CHF) etc…)
  • History of liver disease (as defined by a diagnosis of uncompensated cirrhosis)
  • History of lung disease (including moderate-severe Chronic Obstructive Pulmonary Disease (COPD), interstitial lung disease, or asthma)
  • Known hypersensitivity to yeast-derived products
  • Hemoglobin \< 10 g/dL and hematocrit \< 30%.
  • Abnormal white blood cell count (WBC) count at baseline (\< 3 or \> 12 x 103 cells/mm3, except Project III)
  • Treatment with WBC growth factors (G-CSF or GM-CSF) or immunosuppressive medications (tacrolimus, cyclosporine, mycophenolate, azathioprine, corticosteroids, chlorambucil, cyclophosphamide) within 4 weeks of study (erythropoiesis-stimulating agents will be allowed for Project II and immunosuppression for Project III)
  • Treatment with lithium within 4 weeks of study
  • History of arterial or venous thrombosis

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

sargramostimGranulocyte-Macrophage Colony-Stimulating FactorBlood Specimen Collection

Condition Hierarchy (Ancestors)

Urologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Karl Womer, MD

    University of Florida

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Project I will be used to optimize the dosage and timing of sargramostim administration with regard to the primary and secondary outcomes. Thus, Project II and III treatment will only begin once all 5 Project I participants have completed treatment and the data have been analyzed to guide subsequent dosing
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 21, 2017

First Posted

February 24, 2017

Study Start

February 23, 2017

Primary Completion

September 17, 2018

Study Completion

September 17, 2018

Last Updated

December 31, 2018

Record last verified: 2018-12

Data Sharing

IPD Sharing
Will not share

Locations