Ruxolitinib-Enhanced Haplo HCT for Children and Young Adults With Sickle Cell Disease

Inclusion criteria

• Participants with any genotypic form of SCD aged 12 - 45 years at enrollment with ≥1 of the following:
• History of stroke and/or vasculopathy, including evidence of asymptomatic cerebrovascular disease for pediatric patients.
• Recurrent moderate-severe acute chest syndrome (ACS)
• Recurrent vaso-occlusive pain episodes requiring parenteral analgesia despite the institution of supportive care.
• Need for chronic transfusion therapy to prevent vaso-occlusive complications (i.e. pain, stroke, and ACS).
• For adult patients, an echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥ 2.7 m/sec.
• Participants must have an HLA haploidentical first degree relative (parent, sibling, or half sibling) who is willing and able to donate bone marrow.
• Participants must meet institutional eligibility criteria for HCT.

Exclusion criteria

• Presence of an HLA-matched sibling who is willing and able to donate bone marrow.
• Uncontrolled infection, evidence of active TB, Hepatitis B or C infection, or HIV seropositivity or infection.
• Previous HCT or solid organ transplant.
• CNS revascularization procedure, myocardial infarction, pulmonary embolus or deep vein thrombosis in the past 6 months.
• Use of medications which significantly interfere with ruxolitinib metabolism.
• Known hypersensitivity or severe reaction to ruxolitinib or any component of the conditioning regimen or its excipients.
• Inability to swallow and retain oral medication (use of nasogastric or gastrostomy tube permitted).
• History of malignancy except resected basal cell carcinoma or treated carcinoma in-situ.
• Participation in another clinical trial involving an investigational or off-label use of a drug or device in the past 3 months.
• Currently pregnant or breast feeding.
• Clinically significant, uncontrolled autoimmune disease.
• High-titer anti-donor specific HLA antibodies (without review and approval by Study Chair).
• Participant (or guardian) inability or unwillingness to comply with the dose schedule and study evaluations, comprehend or sign informed consent and utilize a highly effective method of contraception (for participants of child-bearing potential).
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, pose a significant risk to the subject, or interfere with interpretation of study data.