Safety and Efficacy of Prophylactic Defibrotide in Children, Adolescents, and Young Adults With Sickle Cell Disease or Beta Thalassemia Following MAC and Haploidentical Stem Cell Transplantation Utilizing CD34 Enrichment and T-Cell (CD3) Addback

About the study

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.

Study point of contact

Erin Morris, RN
Mitchell S Cairo, MD


4 United States sites


6 to 34 Years


Hemoglobin SC


Phase 2

Study type








participation requirements

– 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

– Abnormal TCD study requiring starting on chronic transfusion therapy and/or exchange

– 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;

participation restrictions

– Patients who are receiving concomitant systemic anticoagulants and/or fibrinolytic

– 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

– 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


  • Los Angeles, California, United States, University of California Los Angeles, 90095 [Recruiting]
  • Ann Arbor, Michigan, United States, University of Michigan, 48109-1274 [Recruiting]
  • Valhalla, New York, United States, New York Medical College, 10595 [Recruiting]
  • Milwaukee, Wisconsin, United States, Medical College of Wisconsin, 53226 [Recruiting]
Last updated 2021-08-02