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Sargramostim for Myeloid Dendritic Cell Deficiency

Primary Purpose

Kidney Diseases, Kidney Transplant

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sargramostim
Blood samples
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Diseases focused on measuring Sargramostim

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Project I: Healthy participants

Project II: Patients with CKD stage IV/V

Project III: kidney transplant patients

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Proportion of patients with adverse events during the intervention.
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.

Full Information

First Posted
February 21, 2017
Last Updated
December 27, 2018
Sponsor
University of Florida
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1. Study Identification

Unique Protocol Identification Number
NCT03063242
Brief Title
Sargramostim for Myeloid Dendritic Cell Deficiency
Official Title
Sargramostim to Reverse Myeloid Dendritic Cell Deficiency
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
Insufficient resources necessary for completion.
Study Start Date
February 23, 2017 (Actual)
Primary Completion Date
September 17, 2018 (Actual)
Study Completion Date
September 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
The overall objective of this project is to study the ability of sargramostim to enhance mDC level and function, including subsequent stimulation of T cell responses, in various human subjects with demonstrated myeloid dendritic cell (mDC) and T cell deficiency. Single center nonrandomized trial with an interrupted time series design involving measures on blood samples from three separate populations before and after administration of sargramostim. The objective is to determine the safety and dose response of sargramostim administration in healthy participants and in patients with chronic kidney disease (CKD) and kidney transplants. Additionally to determine whether reversal of mDC/T cell deficiency by sargramostim results in augmented T cell responses in these three groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Diseases, Kidney Transplant
Keywords
Sargramostim

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Project I: Healthy participants
Arm Type
Experimental
Arm Description
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.
Arm Title
Project II: Patients with CKD stage IV/V
Arm Type
Experimental
Arm Description
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.
Arm Title
Project III: kidney transplant patients
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sargramostim
Other Intervention Name(s)
Leukine®, GM-CSF
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Blood samples
Intervention Description
Blood samples will be drawn at baseline and during each subsequent visit
Primary Outcome Measure Information:
Title
Change in peripheral blood mDC levels
Description
mDC levels to >2.0 x104 mDCs/mL, with the target level defined as levels at or above upper quartile values in healthy controls
Time Frame
Baseline to 2 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients with adverse events during the intervention.
Time Frame
Baseline to 2 weeks
Title
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.
Time Frame
Baseline to 2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karl Womer, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Sargramostim for Myeloid Dendritic Cell Deficiency

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