A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Fludarabine monophosphate; Rituximab; Busulfan; ATG; Cyclophosphamide; Mycophenolate mofetil; Tacrolimus
Intervention description: 180 mg/m2 over 6 days.; 375 mg/m2 on day -13 and day -3; AUC 1000-1200 microM.mt; 2.5 mg/kg for 3 days; 50 mg/kg on day +3; 15 mg/kg q 8 hours; 0.03 mg/kg /d
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Busulfan; Rituximab; Fludarabine; Fludarabine phosphate; Tacrolimus; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: sickle cell; stem cell transplant

Summary:

      Majority of patients who are eligible for allogeneic HSCT for cure of severe sickle cell
      disease lack a matched family donor. This study aims for cure of sickle cell disease by
      performing unrelated donor (outside family) allogeneic HSCT. Donors or unrelated cord blood
      units will be selected from the NMDP database. It is designed to estimate the safety of a
      novel reduced toxicity, yet an immunosuppressive and myeloablative preparative regimen. This
      is meant for patients <21 years old who have severe complications from sickle cell and do not
      have matched sibling donors in the family to undergo stem cell transplant. Patients will
      undergo transplant using unrelated donor stem cells after receiving the protocol therapy.
      They will be followed for 1 year to monitor for engraftment of donor cells and complications
      like graft versus host disease (GVHD), infections and death.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must have sickle cell disease (genotype Hb SS or Sß° thalassemia), AND must have 1
        or more of the following clinical complications related to Sickle cell disease:

          1. A clinically significant neurologic event (stroke) or any neurologic defect lasting
             >24 hours, that is accompanied by an infarct on cerebral MRI.

          2. Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar
             consolidation involving at least 1 complete lung segment associated with acute
             symptoms including fever, chest pain, tachypnea, wheezing or cough) despite adequate
             supportive care measures (example: asthma therapy, hydroxyurea).

          3. History of severe pain episodes defined as 3 or more severe pain events per year in
             the 2 years prior to enrollment despite adequate supportive care measures and
             hydroxyurea trial (i.e. Hydroxyurea non-responders). Pain may occur in typical sites
             associated with vaso-occlusive painful events and cannot be explained by causes other
             than vaso-occlusion mediated by sickle cell disease.

          4. Recurrent priapism.

          5. Osteo-necrosis of multiple joints

          6. Evidence of Pulmonary Hypertension as evidenced by Tricuspid Regurgitation jet
             velocity (TRV) > 2.5 m/s on Echocardiogram.

          7. Red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy.

        Exclusion Criteria:

          1. Invasive bacterial, viral or fungal infections within 1 month prior to starting
             conditioning therapy.

          2. Female patients who are Pregnant (Beta HCG +) or breastfeeding.

          3. HIV positive patients.

          4. Patients with HLA-matched related family donors are not eligible for this study.

          5. Prior myeloablative allogeneic HCT.

          6. Patients on chronic transfusion therapy for ≥ 1 year with evidence of cirrhosis of
             liver on biopsy

          7. Any significant concurrent disease, illness, severe cognitive delay or psychiatric
             disorder that would compromise patient safety or compliance, interfere with consent,
             study participation, follow up, or interpretation of study results.