Sargramostim for Myeloid Dendritic Cell Deficiency

University of Florida

Status and phase: Terminated; Phase 2

Conditions: Kidney Diseases; Kidney Transplant

Treatments: Biological: Blood samples; Drug: Sargramostim

Study type: Interventional

Funder types: Other

Identifiers

NCT03063242

IRB201600815

OCR16461 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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4 participants in 3 patient groups

Project I: Healthy participants

Experimental group

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.

Treatment:

Drug: Sargramostim

Biological: Blood samples

Project II: Patients with CKD stage IV/V

Experimental group

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.

Treatment:

Drug: Sargramostim

Biological: Blood samples

Project III: kidney transplant patients

Experimental group

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.

Treatment:

Drug: Sargramostim

Biological: Blood samples