Sargramostim for Myeloid Dendritic Cell Deficiency

Sargramostim to Reverse Myeloid Dendritic Cell Deficiency

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Diseases; Kidney Transplant
• Intervention / Treatment: Drug: Sargramostim; Biological: Blood samples

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Project I: Healthy participants; 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: Sargramostim; 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.; Other Names: Leukine®, GM-CSF; Biological: Blood samples; Blood samples will be drawn at baseline and during each subsequent visit
EXPERIMENTAL: Project II: Patients with CKD stage IV/V; 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: Sargramostim; 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.; Other Names: Leukine®, GM-CSF; Biological: Blood samples; Blood samples will be drawn at baseline and during each subsequent visit
EXPERIMENTAL: Project III: kidney transplant patients; 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: Sargramostim; 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.; Other Names: Leukine®, GM-CSF; Biological: Blood samples; Blood samples will be drawn at baseline and during each subsequent visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Karl Womer, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 23, 2017
• Primary Completion (ACTUAL): September 17, 2018
• Study Completion (ACTUAL): September 17, 2018

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (ACTUAL): February 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 31, 2018
• Last Update Submitted That Met QC Criteria: December 27, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Sargramostim
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: IRB201600815; OCR16461 (OTHER: University of Florida)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No