Mobilization and Apheresis of Autologous CD34+ Hematopoietic Stem Cells for Patients with RUNX1 Familial Platelet Disorder

Inclusion Criteria

• Are aged ≥ 18 to 75 years * Once a favorable review of safety has been completed by the safety monitoring committee (SMC) in 3 participants aged ≥ 18 years, the study will be opened to participants aged ≥ 12 years
• Are willing and able to provide informed consent, as appropriate (either directly or through a legally authorized representative [LAR])
• Have a confirmed diagnosis of RUNX1-FPD, verified by a Clinical Laboratory Improvement Amendments (CLIA)-certified genetic sequencing report
• Clearance by apheresis team to proceed
• Have systolic blood pressure ≤ 170 mm Hg and diastolic blood pressure ≤ 95 mmHg
• Are eligible for hematopoietic stem cell transplantation (HSCT) per institution requirements
• Have a Lansky (age < 16 years)/Karnofsky performance status of ≥ 70
• Are willing and able to comply with protocol-defined contraceptive requirements
• Have a platelet count ≥ 50,000/μL for initiation of apheresis, assessed within 24 hours prior to the procedure, or, if < 50,000/μL are administered platelets on the day of the collection * If the apheresis team decides that a central venous catheter (CVC) is to be placed, platelet count should be ≥ 50,000 prior to catheter placement
• Have hemoglobin ≥ 7.5 g/dL as assessed within 24 hours prior to the procedure
• Have a white blood cell (WBC) count < 2 × 10^9/L

Exclusion Criteria

• Patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures
• Have uncontrolled bleeding
• Are using supplemental oxygen
• Have known severe splenomegaly (≥ 20 cm)
• Have a diagnosis of myelodysplastic syndrome (MDS) or hematologic malignancies, as defined by World Health Organization (WHO) hematolymphoid tumor classification fifth edition (Khourey et al 2022)
• Have recent prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ * Note: Cancer treated with curative intent < 5 years previously may be allowed following approval from the study investigator. Cancer treated with curative intent > 5 years previously is allowed
• Have any prior or current myeloproliferative or a significant coagulation or immunodeficiency disorder
• Have advanced liver disease, defined as any of the following: * Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value > 5× the upper limit of normal (ULN) at screening * Screening prothrombin time (PT) or partial thromboplastin time (PTT) > 1.5 × ULN
• Have had prior HSCT or gene therapy
• Have history of concomitant sickle cell disease
• Have been treated with an investigational drug within 30 days of screening or 5 half-lives (whichever is longer)
• Have a positive test result for HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) at screening * Participants with positive hepatitis B core antibody (HbcAb) and/or hepatitis B-e antibody (HbeAb) are eligible provided viral load is negative by quantitative polymerase chain reaction (qPCR). * Participants who are positive for anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load by qPCR
• Have a positive infectious disease panel at screening for human T-lymphotropic virus 1 or 2 (HTLV-1 and HTLV-2), or syphilis (rapid plasma 24 reagin [RPR])
• Have clinically significant and active bacterial, viral, fungal, or parasitic infection at screening
• Have a left ventricular ejection fraction < 45%
• Have a screening estimated glomerular filtration rate < 60 mL/min/1.73 m^2
• Have a diagnosis of a significant psychiatric disorder that could seriously impede the ability to participate in the study
• For women of childbearing potential: are pregnant or breastfeeding or lack adequate contraception
• Are unable to comply with the study procedures, as assessed by the investigator