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

Conditions

• Idiopathic CD4-Positive
• T-Lymphocytopenia

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Accepted

Interventions

• Filgrastim — BIOLOGICAL
  10 microgram/kg daily for 5 days, Subcutaneous injection.
• Plerixafor — DRUG
  IV injection 0.24 mg/kg as a single dose, 11 hours prior to apheresis

Study Details

Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (\<300/mm3) 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-1 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 Dates

Start date

Jan 15, 2014

Status verified

May 2026

Primary completion

Oct 31, 2026

Completion

Oct 31, 2026

Study Design

Enrollment

40 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: Filgrastim
  ICL and healthy volunteers will be given 10 microgram/kg daily for 5 days administered according to a vial-based algorithm to reduce wastage and increase the G-CSF dose given to lighter-weight donors to improve CD34+ yields
• Experimental: Plerixafor
  ICL and healthy volunteers will be given 0.24 mg/kg as a single dose (maximum dose: 40 mg) 11 hours prior to apheresis

Primary Outcome Measure

To mobilize CD34+ HPCs in ICL patients and healthy volunteers for collection and transfer into immunocompromised mice to investigate thymic development, survival, and trafficking of these cells in murine lymphoid and non-lymphoid organs [ Time Frame: Throughout the study ]

Central Contacts

• Irini Sereti, M.D.
  (301) 496-5533
  [email protected]

Locations (1)

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