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Sargramostim for Myeloid Dendritic Cell Deficiency

Sponsor
University of Florida (Other)
Overall Status
Terminated
CT.gov ID
NCT03063242
Collaborator
(none)
4
Enrollment
1
Location
3
Arms
18.8
Actual Duration (Months)
0.2
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
4 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention 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 dosingProject 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)
Primary Purpose:
Treatment
Official Title:
Sargramostim to Reverse Myeloid Dendritic Cell Deficiency
Actual Study Start Date :
Feb 23, 2017
Actual Primary Completion Date :
Sep 17, 2018
Actual Study Completion Date :
Sep 17, 2018

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Change in peripheral blood mDC levels [Baseline to 2 weeks]

      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

    1. Proportion of patients with adverse events during the intervention. [Baseline to 2 weeks]

    2. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Florida Gainesville Florida United States 32610

    Sponsors and Collaborators

    • University of Florida

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT03063242
    Other Study ID Numbers:
    • IRB201600815
    • OCR16461
    First Posted:
    Feb 24, 2017
    Last Update Posted:
    Dec 31, 2018
    Last Verified:
    Dec 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University of Florida
    Sargramostim
    Additional relevant MeSH terms:
    Kidney Diseases
    Sargramostim

    Study Results

    No Results Posted as of Dec 31, 2018