Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)

Inclusion Criteria: * Adult patients at least 18 years old * Diagnosis of sickle cell disease (hemoglobin SS or Sβ0 genotype) * Receiving automated RBC exchanges via apheresis-capable central venous access or willing to have apheresis-capable venous access placed. * Able to hold hydroxyurea, voxelotor, and/or crizanlizumab for at least 60 days prior to mobilization * Able to hold iron chelation for at least 7 days prior to mobilization * ECOG performance status ≤ 1 * Normal bone marrow and organ function at screening as defined below: * Leukocytes ≥ 2,000/uL * Absolute neutrophil count ≥ 1,500/uL * Platelets ≥ 75,000/uL * AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN at time of screening * Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault * Baseline oxygen saturation ≥ 92% on room air * Left ventricular ejection fraction (LVEF) ≥ 45% (Of note, transthoracic echocardiogram (TTE) will not be required for study. However, if the treating physician has clinical concerns for active cardiac disease for which a TTE is clinically warranted as standard of care, then an EF of ≥ 45% will be required). * The effects of motixafortide and natalizumab on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation, and 3 months after completion of the study. Should a woman become pregnant o…