Sargramostim for Myeloid Dendritic Cell Deficiency

NCT ID: NCT03063242

Last Updated: 2018-12-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-23
• Study Completion Date: 2018-09-17

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.

Conditions

Kidney Diseases; Kidney Transplant

Keywords

Sargramostim

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sargramostim

Intervention Type: DRUG

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.

Blood samples

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

Sargramostim

Intervention Type: DRUG

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.

Blood samples

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

Sargramostim

Intervention Type: DRUG

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.

Blood samples

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: DRUG

Blood samples

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Leukine®, GM-CSF

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karl Womer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Other Identifiers

OCR16461

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201600815

Identifier Type: -

Identifier Source: org_study_id