Using Defibrotide to Improve Stem Cell Transplant Outcomes for Sickle Cell Disease

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

This study is testing if giving Defibrotide before a stem cell transplant can help people with sickle cell disease avoid serious complications and have better outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 6 Months to 34 Years
• Sex: All
• Sponsor: New York Medical College (Academic / other)
• Locations: 4 sites (Los Angeles, California and 3 other locations)
• Trial ID: NCT02675959 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of Defibrotide as a preventive treatment for patients with sickle cell disease undergoing haploidentical stem cell transplantation. The study focuses on patients at high risk for developing sinusoidal obstructive syndrome (SOS), a serious complication associated with this procedure. By administering Defibrotide prophylactically, the trial aims to reduce the incidence of SOS and improve overall transplant outcomes. This is a follow-up to a previous trial that laid the groundwork for this investigation.

Who should consider this trial

Good fit: Ideal candidates include individuals with severe forms of sickle cell disease who have experienced significant complications such as strokes or acute chest syndrome.

Not a fit: Patients with mild sickle cell disease or those who do not meet the high-risk criteria for complications may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce complications and improve survival rates for patients with sickle cell disease undergoing stem cell transplantation.

How similar studies have performed: Previous studies have shown promising results with similar approaches, particularly in the use of Defibrotide for preventing SOS in high-risk patients.

Eligibility criteria

Inclusion Criteria:

* 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;

Exclusion 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

Where this trial is running

Los Angeles, California and 3 other locations

• University of California Los Angeles — Los Angeles, California, United States (Recruiting)
• University of Florida — Gainesville, Florida, United States (Recruiting)
• New York Medical College — Valhalla, New York, United States (Recruiting)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Mitchell Cairo, MD — New York Medical College
• Study coordinator: Mitchell S Cairo, MD

Conditions Sickle Cell Disease; stem cell transplantation; sickle cell disease; haploidentical; defibrotide