Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine Models

Recruiting now · Phase 2

Conditions studied: Idiopathic CD4-Positive, T-Lymphocytopenia

In brief

Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (\<300/mm\^3) without evidence of HIV infection or other known immunodeficiency. Patients with ICL are at risk for opportunistic infections typically associated with HIV/AIDS such as disseminated cryptococcal infection and severe human papillomavirus-related dysplasia. More than 20 years since the description of ICL, its etiology, pathogenesis, and management remain unclear. In this study we propose to administer the combination of granulocyte colony stimulating factor (G-CSF) and plerixafor to ICL patients and healthy volunteers with the objective of harvesting mobilized CD34+ hematopoietic progenitor cells (HPCs) by apheresis for transfer into immunocompromised mice and for study with in vitro assays. The mice studies would serve to investigate thymic development, survival, and trafficking of the mobilized human cells within murine lymphoid and non-lymphoid organs. HPCs are used for various therapies and there is an increasing use of agents that stimulate the bone marrow to produce progenitor cells and move them into the bloodstream where they may be harvested by apheresis. Not all patients respond to GCSF with vigorous HPC mobilization. The binding of chemokine receptor CXCR4 to stromal cell derived factor (SDF-1 or CXCL12) is an important interaction between a hematopoietic progenitor cell and its marrow environment. Plerixafor is a CXCR4 inhibitor which blocks binding to SDF-1alpha resulting in the release of hematopoietic progenitor cells (CD34+) into peripheral circulation. In pharmacodynamic studies of plerixafor in conjunction with G-CSF compared to G-CSF and placebo, a two-fold increase in CD34+ cell count was observed. Due to the important role CXCR4 plays in immune cell trafficking and its potential role in the pathogenesis of ICL, we propose as a secondary objective to assess peripheral CD4 T cell and CD34+ hematopoietic progenitor cell numbers and functions in ICL patients compared to controls following G-CSF and plerixafor administration. Study participants will be screened within 12 weeks prior to the study period. Eligible participants will receive G-CSF for 5 days with hospitalization on Day 4 for plerixafor injection followed by apheresis on Day 5. Participants will return for examinations and blood draws on Days 8 and 12.

Key facts

Study ID

NCT02015013

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

40

Starts

2014-01-15

Expected to finish

2030-10-31

Last updated by the study team

2026-08-03

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

• Active uncontrolled infection at the time of enrollment
• Current autoimmune conditions requiring systemic (oral, injection, or other parenteral) therapy
• History of vasculitis
• Current or history of hematologic or lymphoid malignancy (leukemia)
• History of splenomegaly or current splenomegaly on exam or ultrasound (for ICL patients and patients with similar immunological defects)
• History of hypersensitivity to plerixafor and/or G-CSF
• Recent use of a systemic immune-modulatory agent which, in the opinion of the investigator, may interfere with the scientific integrity of the study
• Thrombocytopenia (platelets <100,000 cells/microL)
• Hepatitis B and C seropositivity (HBsAg positive and anti-HCV positive) Need for anticoagulant medication (e.g., warfarin, heparin), other than aspirin, clopidogrel, or other antiplatelet agent
• Creatinine clearance <50 mL/min including end-stage renal disease requiring hemodialysis
• Symptomatic coronary artery disease
• Uncontrolled hypertension (i.e., resting systolic blood pressure >160 mmHg or resting diastolic blood pressure >90 mmHg) despite pharmacologic antihypertensive treatment confirmed with a second blood pressure measurement done later on the same day
• Cardiac, pulmonary, thyroid, renal, hepatic, neurological (central or peripheral) disease or disorder of hemostasis requiring therapy and considered to be significant by the protocol team
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
• Currently receiving lithium due to contraindication of co-administration of G-CSF with lithium
• Past or current psychiatric illness that, in the opinion of the investigator, would interfere with protocol adherence or the ability to give written informed consent
• Any illness or condition that, in the opinion of the investigator, may substantially increase the risk associated with participation in the study or compromise the scientific objectives
• Participation in a clinical protocol which includes an intervention that, in the opinion of the investigator, may affect the results of the current study
• Previous history of anaphylactic reaction to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Female who is breast-feeding.

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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