Bone Marrow Failure Syndrome
Conditions
Brief summary
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
DRUGFilgrastim
Administered twice daily dose starting on day 1 for 5 days.
DRUGPlerixafor
Administered on day 5 via IV.
PROCEDURELeukapheresis
Peripheral venous access or through a central venous catheter approximately 4-5 hours after the dose of plerixafor is given.
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 25 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events following filgrastim plus plerixafor administration | From initiation of drug administration through Day +7 to +10 follow-up | Safety will be assessed by the incidence, type, and severity of adverse events occurring after administration of filgrastim plus plerixafor in participants with bone marrow failure syndromes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants achieving peripheral blood CD34+ counts ≥5 cells/µL | From initiation of plerixafor administration through completion of apheresis, or 6 hours after drug administration if apheresis is not performed | Feasibility of hematopoietic stem and progenitor cell mobilization will be assessed by peripheral blood CD34+ cell counts measured after plerixafor administration and prior to or during apheresis. |
| Peripheral blood CD34+ kinetics following filgrastim plus plerixafor administration | After plerixafor administration through completion of apheresis, or 6 hours after drug administration if apheresis is not performed | Peripheral blood CD34+ cell counts will be measured after plerixafor administration and prior to or during apheresis. |
| Observed CD34+ cell yield after 1 blood volume apheresis | At completion of 1 blood volume apheresis on Day 5 | CD34+ cell yield (CD34+ cells/kg) collected after processing 1 blood volume during apheresis following filgrastim plus plerixafor administration. |
| Estimated total CD34+ cell yield from projected full-volume apheresis | At completion of 1 blood volume apheresis on Day 5 | Estimated total CD34+ cell yield (CD34+ cells/kg) projected from the observed yield after processing 1 blood volume during apheresis. |
Countries
United States
Contacts
CONTACTAlexis Leonard, MD
PRINCIPAL_INVESTIGATORAlexis Leonard, MD
St. Jude Children's Research Hospital
Outcome results
None listed