Stem Cell Mobilization and Apheresis for Life-threatening Blood Disorders

Overview

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).

Detailed description

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.

Interventions

• Drug Filgrastim
  Administered twice daily dose starting on day 1 for 5 days.
• Drug Plerixafor
  Administered on day 5 via IV.
• Procedure Leukapheresis
  Peripheral venous access or through a central venous catheter approximately 4-5 hours after the dose of plerixafor is given.

Primary outcome measures

• Incidence of treatment-emergent adverse events following filgrastim plus plerixafor administration [Time frame: From initiation of drug administration through Day +7 to +10 follow-up]

Secondary outcome measures (4)

• Number of participants achieving peripheral blood CD34+ counts ≥5 cells/µL [Time frame: From initiation of plerixafor administration through completion of apheresis, or 6 hours after drug administration if apheresis is not performed]
• Peripheral blood CD34+ kinetics following filgrastim plus plerixafor administration [Time frame: After plerixafor administration through completion of apheresis, or 6 hours after drug administration if apheresis is not performed]
• Observed CD34+ cell yield after 1 blood volume apheresis [Time frame: At completion of 1 blood volume apheresis on Day 5]
• Estimated total CD34+ cell yield from projected full-volume apheresis [Time frame: At completion of 1 blood volume apheresis on Day 5]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

United States · 1 center

• Saint Jude Children's Research Hospital — Memphis

Identifiers

NCT: NCT07585136 · BDSTEM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗