Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York Medical College
• Collaborators: Baylor College of Medicine; Children's Hospital Los Angeles; Dana-Farber Cancer Institute; Johns Hopkins University; Medical College of Wisconsin; Tufts Medical Center; University of California, Los Angeles; University of Michigan
• Treatments: Defibrotide

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