Stem Cell Mobilization and Apheresis for Life-threatening Blood Disorders

Обзор

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).

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (4)

• Number of participants achieving peripheral blood CD34+ counts ≥5 cells/µL [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: At completion of 1 blood volume apheresis on Day 5]
• Estimated total CD34+ cell yield from projected full-volume apheresis [Срок оценки: At completion of 1 blood volume apheresis on Day 5]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Saint Jude Children's Research Hospital — Memphis

Идентификаторы

NCT: NCT07585136 · BDSTEM

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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