The purpose of this study is to investigate mobilization and collection of HSPCs in patients with bone marrow failure syndromes (BMFS) using granulocyte-colony stimulating factor (otherwise known as Filgrastim) with plerixafor to demonstrate safety and feasibility of collecting HSPCs to advance gene therapy.

Primary objective:

- To characterize the safety of Filgrastim plus plerixafor in participants with bone marrow failure syndromes as determined by the incidence of adverse events (AEs).

Secondary Objectives:

• To characterize the feasibility of HSPC mobilization using Filgrastim plus plerixafor as determined by peripheral blood CD34+ counts.
• To measure the mobilization effects of Filgrastim plus plerixafor in the peripheral blood in participants as determined by peak peripheral blood CD34+ counts.
• To estimate efficacy of Filgrastim plus plerixafor for HSPC mobilization and apheresis collection in participants as determined by the yield of CD34+ cells (CD34+ cells/kg).

This is a phase I, open-label, single-center study to evaluate the safety of Filgrastim plus plerixafor stem cell mobilization and apheresis in patients with BMFS. This study will include a screening period with labs, physical examination, and bone marrow evaluation at least 6 months prior to mobilization and apheresis, an intervention period that includes mobilization and apheresis of patient HSPCs, and outpatient follow-up within 7-10 days after intervention. Study staff will follow up with the participant via telephone approximately 30 days after mobilization and apheresis. A bone marrow evaluation will be done within 6 months post-intervention.

Inclusion Criteria:

• Participants with a bone marrow failure syndrome with an identified genetic cause willing to donate autologous HSPCs for advancing gene therapy

• Age ≥ 18 years - 25 years

• The following hematological parameters need to be met (regardless of transfusion or growth factor support)

  • Hb > 8 g/dL
  • ANC > 500/mm3
  • Platelet > 30,000/mm3

• Bone marrow evaluation within the preceding 6 months prior to mobilization and apheresis

• Participants should either have a central venous catheter (CVC) in place, be able to undergo apheresis without requiring a CVC, or agree to having a temporary apheresis catheter placed

• Karnofsky score >80

• Negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1/II

• Female participants of childbearing age should have a negative serum pregnancy test within one week of beginning Filgrastim and plerixafor administration

Exclusion Criteria:

• Participant with sickle cell disease
• Participant who has had a prior autologous or allogeneic HSCT
• Active viral, bacterial, fungal, or parasitic infection
• Total bilirubin >2.5x ULN or transaminases >5x ULN
• Moderate or severe renal failure defined as serum/plasma creatinine >1.5 mg/dL and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 based on the CKD-Epi equation or the St. Jude equation
• Diagnosis of MDS or other hematologic malignancy
• History of malignancy
• Known allergy to or contraindication for Filgrastim or plerixafor administration, or medications routinely administered during apheresis
• Splenomegaly (size greater than upper limit of normal on examination)
• Any disease or concomitant process that is not compatible with the study as per investigator opinion
• Concomitant treatment with alternative investigational agent or participation in another clinical trial with an investigational drug within 5 half-lives of the investigational agent
• Unwillingness to use a highly effective method of contraception for 1 month after plerixafor or GCSF
• Pregnancy
• Inability or unwillingness of research participant to give written informed consent.

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Data will be made available at the time of article publication.

Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.