Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease
This is a follow-up trial to NYMC 526 (NCT01461837) to assess the safety, efficacy and toxicity of administering Defibrotide prophylaxis for high-risk sickle cell or beta thalassemia patients undergoing a familial haploidentical allogeneic stem cell transplantation with CD34 enrichment and T-cell addback. This patient population historically has a risk of developing sinusoidal obstructive syndrome (SOS) and Defibrotide has demonstrated efficacy in treatment of SOS. The Funding Source is FDA OOPD.
- Disease: Homozygous Hemoglobin S Disease, or Hemoglobin S B0/+ thalassemia, or Hemoglobin SC Disease, or Beta thalassemia intermedia/majora
- Patients must demonstrate one or more of the following Sickle Cell Disease Complications (or patients in Cohort 2 can meet other high risk criteria instead)
- Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
- Acute chest syndrome in the preceding two year period prior to enrollment that have failed, been non-compliant or declined hydroxyurea treatment, or prior to chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis.
- Recurrent painful events (at least 3 in the 2 years prior to enrollment or prior to chronic chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis).
- Abnormal TCD study requiring starting on chronic transfusion therapy and/or exchange transfusions.
- At least one silent infarct lesion on a MRI scan of the head. Or (directly or probably related to SCD)
- Sickle Cell nephropathy;
- Splenic sequestration requiring RBC transfusion;
- Aplastic crisis requiring RBC transfusion;
- Avascular necrosis of the hip diagnosed by MRI;
- Two episodes or more of leg ulcerations;
- Recurrent priapism .
- Infant dactylitis.
- OR for Cohort #2 ONLY: Patient must be between 18 and 34.99 years of age, patients must demonstrate at least two of the following:
- WBC > 13,500 cells/microliter at baseline when not acutely ill (on two separate occasions) > 2 weeks from a VOC event or hospitalization.
- Tricuspid Regurgitant Jet Velocity (TRV) > 3.0 m/s
- Requiring Chronic Monthly Transfusions ( > 12 transfusions in the 12 months)
- History of sepsis
- N-terminal pro-brain natriuretic peptide (NT-proBNP) > 160 ng/L at clinical baseline when not acutely ill or hospitalized.
- all patients must meet disease, age, organ function and donor criteria;
- Patients who are receiving concomitant systemic anticoagulants and/or fibrinolytic therapies.
- Patients with a previously known hypersensitivity reaction to defibrotide.
- Females who are pregnant or breast-feeding are not eligible
- SCD Patients with documented uncontrolled infection at the time of study entry are not eligible.
- SCD patients who have an unaffected HLA matched family donor willing to proceed to donation will not be eligible for this study.
- Karnofsky or Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
- Demonstrated lack of compliance with medical care.
- Patients with clinically significant fibrosis or cirrhosis of the liver will not be eligible.
- Patients who have previously received a HSCT will not be eligible.
- Patients with contraindications to the use of defibrotide
Join this Trial
- UCLA Westwood