RECRUITING

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

Conditions

Sickle Cell Disease stem cell transplantation haploidentical defibrotide

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2017-07-01

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02675959

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:6 Months to 34 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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;	* 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

Inclusion Criteria

Exclusion 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;

* 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

Contacts and Locations

Study Contact

Mitchell S Cairo, MD

CONTACT

914-594-2150

Mitchell_Cairo@nymc.edu

Erin Morris, RN

CONTACT

714-964-5359

erin_morris@nymc.edu

Principal Investigator

Mitchell Cairo, MD

PRINCIPAL_INVESTIGATOR

New York Medical College

Study Locations (Sites)

University of California Los Angeles

Los Angeles, California, 90095

United States

University of Florida

Gainesville, Florida, 32610-0278

United States

New York Medical College

Valhalla, New York, 10595

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: New York Medical College

Mitchell Cairo, MD, PRINCIPAL_INVESTIGATOR, New York Medical College

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-07-01

Study Completion Date2025-12

Study Record Updates

Study Start Date2017-07-01

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

stem cell transplantation
sickle cell disease
haploidentical
defibrotide

Additional Relevant MeSH Terms

Sickle Cell Disease