Motixafortide with and without Natalizumab for Mobilization of Hematopoietic Stem Cells for Patients Receiving Gene Therapies for Sickle Cell Disease

Inclusion Criteria

• Adult patients aged 18-40 years old
• Diagnosis of sickle cell disease (hemoglobin SS or Sbeta^0 genotype)
• Receiving automated red blood cell (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
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Leukocytes >= 2,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 75,000/uL
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x institutional upper limits of normal (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 or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 3 months after completion of the study
• Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

• Patients may not have a history of receiving the following therapies: prior hematopoietic cell transplant (HCT) or prior gene therapy
• Currently receiving concomitant immunosuppressants including 6-mercaptopurine, azathioprine, cyclosporine, methotrexate or concomitant inhibitors of tumor necrosis factor (TNF)-alpha
• Patient may not have a history of significant alloantibodies which, in the opinion of the treating physician and study investigator, significantly increase the risk of participation in this clinical trial
• Currently receiving any other investigational agents
• A history of progressive multifocal leukoencephalopathy
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to motixafortide or natalizumab
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including but not limited to human immunodeficiency virus [HIV], active/untreated Hepatitis C and/or active/untreated Hepatitis B), ongoing/active vaso-occlusive pain crisis or uncontrolled sickle cell disease (SCD)-related symptoms, symptomatic congestive heart failure, cerebrovascular accident, unstable angina pectoris, or cardiac arrhythmia
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum/urine pregnancy test within 7 days of study entry and prior to each study agent administration/HSC mobilization
• Determined by the investigator to be unable or unlikely to comply with the study procedures included in this protocol