Idiopathic CD4-PositivePhase 2NCT02015013
Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine Models
A Phase 2 study testing Filgrastim and Plerixafor in people with Idiopathic CD4-Positive and T-Lymphocytopenia, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Idiopathic CD4-Positive, T-Lymphocytopenia
- What is being tested?
- Filgrastim and Plerixafor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2014to 31 Oct 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ICL patients:
- Documented history of idiopathic CD4 lymphocytopenia as defined by CD4 T cell count <300 cells/microL or <20% of total T lymphocytes on 2 occasions at least 6 weeks apart in the absence of any illness or medications accounting for CD4 lymphocytopenia. Although the protocol will primarily enroll ICL patients who are lymphopenic at the time of enrollment, up to three patients who had clear documentation of ICL in the past and are currently not lymphopenic may still be enrolled for comparative purposes. For similar comparative purposes, we may enroll up to five participants with known or unknown immunological-defects that may be affecting lymphocyte homeostasis or function, irrespective of CD4 T cell counts, including people with history of infectious diseases or other conditions that are typically seen in ICL [i.e. cryptococcal diseases, mycobacterial diseases, HPV-related diseases, histoplasmosis, progressive multifocal leukoencephalopathy or herpesviruses associated diseases (Varicella-zoster virus diseases, cytomegalovirus diseases, or Kaposi's sarcoma) and autoimmune diseases].
- Hemoglobin >=9 g/dL
- Human T-lymphotropic virus Type 1 (HTLV-1) and HTLV-2 seronegative Persons with documented history of ICL in whom genetic analysis revealed inherited defects that are either known or suspected to be involved in development, maturation, or homeostasis of hematopoietic cells
- Healthy volunteers: white blood cell count >2500/microL and hemoglobin >=12.5 g/dL
- ICL patients, patients with similar immunological defects, and healthy volunteers:
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- Age 18-65 years
- Weight at least 50 kg but less than 167 kg and <175% ideal body weight (due to lack of data regarding appropriate dosing of plerixafor)
- Ability to give informed consent
- Capacity and willingness to adhere to study procedures, including scheduled follow-up visits
- Willingness to have blood samples stored for future research
- Willingness to undergo HLA testing
- Established primary care provider
- HIV-1 and HIV-2 seronegativity and plasma HIV-1 RNA polymerase chain reaction (PCR) below the limit of detection
- Adequate venous access to allow leukapheresis without use of a central line or a large volume blood draw
- Participant agrees to be heterosexually inactive or consistently use effective birth control (e.g., barrier methods, oral contraceptives, intrauterine devices, vasectomy) for the duration of study participation and for approximately 8 weeks after the last dose of G-CSF. This is necessary for both male and female participants.
- For women of childbearing potential:
- Negative serum or urine pregnancy test
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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....
Read the detailed description
Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (<300/3microL) without evidence of HIV infection or other known immunodeficiency. Patients with ICL are at risk for opportunistic infections typically associated with HIV/AIDS and other immunological defects 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 G-CSF 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 HPCs (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 plerixafor injection on Day 4, followed by apheresis or large volume blood draw (120 cc) on Day 5. Participants will return for examinations and blood draws on Days 8 and 12.
- Conditions
- Idiopathic CD4-Positive, T-Lymphocytopenia
- Being tested
- Filgrastim, Plerixafor
- Keywords
- Leukapheresis, Progenitor Cells
- Medical subject headings
- T-Lymphocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FilgrastimBiological
10 microgram/kg daily for 5 days, Subcutaneous injection.
PlerixaforDrug
IV injection 0.24 mg/kg as a single dose, 11 hours prior to apheresis
| Study group | Role | What they receive |
|---|---|---|
| Filgrastim | Experimental | 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 Receives: Biological: Filgrastim |
| Plerixafor | Experimental | ICL and healthy volunteers will be given 0.24 mg/kg as a single dose (maximum dose: 40 mg) 11 hours prior to apheresis Receives: Drug: Plerixafor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Collection of CD34+ cells from ICL patients and healthy volunteers to investigate thymic development, survival, and trafficking of these mobilized cells in the lymphoid and non lymphoid organs of mice.
Measured: Throughout the study
Secondary outcomes (1)
To assess peripheral CD4 T cell and CD34+ HPC numbers and functions in ICL subjects compared to controls following G CSF and plerixafor administration
Collection of peripheral CD4 T cells and CD34+ HSCs for comparison of number and function of these cell types in ICL patients and healthy volunteers. The function of progenitor cells will be measured as multipotency.
Measured: Throughout the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2013 (estimated)
- Study start15 Jan 2014
- Primary completion31 Oct 2030 (estimated)
- Study completion31 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Idiopathic CD4-PositiveStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irini Sereti, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02015013
- Sponsor's protocol ID
- 140020
- Other IDs
- 14-I-0020
- Status last verified
- 30 Jul 2026
- First submitted
- 13 Dec 2013
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underline the results reported in this article, after deidentification
Publications
Isgro A, Sirianni MC, Gramiccioni C, Mezzaroma I, Fantauzzi A, Aiuti F. Idiopathic CD4+ lymphocytopenia may be due to decreased bone marrow clonogenic capability. Int Arch Allergy Immunol. 2005 Apr;136(4):379-84. doi: 10.1159/000084258. Epub 2005 Mar 2.
PubMed 15746558Fruhwirth M, Clodi K, Heitger A, Neu N. Lymphocyte diversity in a 9-year-old boy with idiopathic CD4+ T cell lymphocytopenia. Int Arch Allergy Immunol. 2001 May;125(1):80-5. doi: 10.1159/000053800.
PubMed 11385292Hubert P, Bergeron F, Ferreira V, Seligmann M, Oksenhendler E, Debre P, Autran B. Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia. Int Immunol. 2000 Apr;12(4):449-57. doi: 10.1093/intimm/12.4.449.
PubMed 10744646