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

  • STATUS
    Recruiting
  • End date
    Oct 31, 2026
  • participants needed
    40
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 22 September 2022
Accepts healthy volunteers

Summary

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.

...

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 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 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 hospitalization on Day 4 for plerixafor injection 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.

Details
Condition Idiopathic CD4-Positive, T-Lymphocytopenia
Treatment filgrastim, Plerixafor
Clinical Study IdentifierNCT02015013
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on22 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Hemoglobin greater than or equal to 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 greater than or
equal to 12.5 g/dL
ICL patients and healthy volunteers
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
Willingness to have blood samples stored for future research
Capacity and willingness to adhere to study procedures, including scheduled follow-up
Willingness to undergo HLA testing
visits
Willingness to be hospitalized for approximately 24 hours
Established primary care provider
HIV-1 and HIV-2 seronegativity and plasma HIV-1 RNA polymerase chain reaction (PCR)
below the limit of detection
For women of childbearing potential
Adequate venous access to allow leukapheresis without use of a central line or a large
Negative serum or urine pregnancy test
volume blood draw
Participant agrees to be heterosexually inactive or consistently use effective birth
control (e.g., barrier methods, oral contraceptives, intrauterine devices, vasesctomy)
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

Exclusion Criteria

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)
History of hypersensitivity to plerixafor and/or G-CSF
Systemic immune-modulatory agent within the past 6 months
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 of child-bearing potential who is breast-feeding
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note