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

Phase 2

Recruiting

• Conditions: Sickle Cell Disease
• Interventions: Drug: Defibrotide

• Registration Number: NCT02675959
• Lead Sponsor: New York Medical College

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-01-22
• Study First Submitted QC: 2016-02-02
• Study First Posted: 2016-02-05
• Study Start: 2017-07-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-23
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Defibrotide prophylaxis	Defibrotide	defibrotide will be given prior to and during myeloablative immunotherapy conditioning (MAIC) followed by familial haploidentical (FHI) allogeneic stem cell transplantation (AlloSCT) with CD34 enrichment and t-cell addback in patients with high-risk sickle cell disease or beta thalassemia to reduced the risk and rate of the development of sinusoidal obstructive syndrome (SOS).

Primary Outcome Measures

Name	Time	Method
All patients will be monitored for the development of SOS.	1 year	All patients will get daily lab values while in patients and then as needed to monitor for elevation in liver function tests and other abnormal chemistry or hematology values. Imaging on the liver will be performed as needed to determine if they develop SOS with defibrotide.
All patients will be monitored for known and unknown side effects of defibrotide with daily physical exams while in the hospital and then as needed in addition to daily laboratory values including chemistries, hematology labs as needed	100 days	Patients will be given Defibrotide prophylaxis starting 10 days before the stem cell infusion at 6.25 mg/kg IV q6h and continue through Day +21.

Trial Locations

Locations (4)

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

New York Medical College; 🇺🇸 Valhalla, New York, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States