A Blood Stem Cell Transplant for Sickle Cell Disease

This is a pilot study to determine the safety and feasibility of the COH-MC-17 regimen and ability of the regimen to induce a mixed chimeric status in severe sickle cell disease patients (hemoglobin SS or S-βº Thalassemia). The COH-MC-17 regimen consists of a non-myeloablative regimen (cyclophosphamide, pentostatin and rabbit-anti-thymocyte globulin (ATG)) followed by a CD4+ T-cell-depleted haploidentical hematopoietic cell transplant (HaploHCT).

Inclusion:

• Confirmed diagnosis of hemoglobin SS or S-βº Thalassemia sickle cell disease
• Severe disease status as defined by presence of one or more of the following:

• Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours; or increased transcranial Doppler velocity (>200 m/s). A stroke is defined as a sudden neurologic change lasting more than 24 hours that is accompanied by cerebral magnetic resonance imaging (MRI) changes.
• History of ≥ 1 episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea).
• History of ≥ 2 severe vaso-occlusive pain crises (VOC) per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea). A severe VOC is defined as an episode of pain lasting more than 2 hours severe enough to require care at a medical facility. Note that priapism that lasts more than 2 hours and requires care at a medical facility is also considered a VOC.
• Osteonecrosis of ≥ 2 joints despite the institution of supportive care measures.
• Prior treatment with regular RBC transfusion therapy, defined as receiving ≥ 8 transfusions per year for > 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
• No HLA matched sibling or 10/10 matched unrelated donor
• Related donor who:

• Is genotypically haploidentical on HLA-A, B, C and DRB1 loci AND
• Meets institutional criteria
• Failed prior hydroxyurea therapy or have intolerance to hydroxyurea
• Meets protocol specified organ function criteria
• Women of childbearing potential or sexually active male: Agreement to use adequate contraception prior to study entry and 6 months post-transplant.

Exclusion criteria

• Prior stem cell transplant
• Prior bone marrow transplant
• Concurrent other investigational agents, chemotherapy, biological therapy or radiation therapy
• Planned use of moderate and strong CYP3A4 inhibitors
• Active infection
• Major surgery within the last 30 days
• Clinically significant liver fibrosis or cirrhosis if on chronic transfusion therapy > 6 months
• Active malignancy (other than non-melanoma skin cancers)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any in the pre- or post-transplant regimen.
• Women of childbearing potential: pregnant or breastfeeding