Eligibility
All studies to determine eligibility must be performed within 60 days prior to starting conditioning therapy unless otherwise indicated below. The eligibility criteria listed below are interpreted literally and cannot be waived.
Inclusion
In order to qualify for this clinical trial, the patient must
Have one or more of the following Sickle Cell Disease Complications:
OR for Cohort #2 ONLY: Patient must be between 21 and 34.99 years of age, patients must demonstrate at least two of the following:
Minimum of one episode of acute chest syndrome…
Recurrent painful events…. Remove “These painful events may have been treated in any setting; however, the events, including events that were managed at home, will be considered for eligibility only if there is documentation of the event in a clinical record that may be reviewed by the investigator.”
Abnormal TCD study – unchanged
At least one silent infarct lesion – unchanged
Additional high risk criteria related to sickle cell nephropathy, splenic sequestration, aplastic crisis, avascular necrosis, leg
ulcerations, recurrent priapism or infant dactylitis may be eligible.
Exclusion
In order to qualify for this clinical trial, the patient must not:
Inclusion
In order to qualify for this clinical trial, the patient must
- Have Homozygous Hemoglobin S Disease (HbSS) or Hemoglobin S β0/+ thalassemia or Hemoglobin SC Disease
- Patient must be between 1 and 17.99 years of age (cohort #1), or between 18 and 34.99 years of age (cohort #2)
Have one or more of the following Sickle Cell Disease Complications:
- Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
- Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least one complete lung segment associated with acute symptoms including fever >38.5, chest pain, tachypnea, intercostal retractions, nasal flaring, use of accessory muscles of respiration, wheezing, rales, or cough not attributable to asthma or bronchiolitis) 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. The acute chest syndrome event occurred despite adequate supportive care measures (i.e. despite the use of supportive care and interventions including asthma therapy and/or hydroxyurea; patients who decline hydroxyurea or non-compliant with this therapy are eligible if they meet the other pulmonary criteria defined above for inclusion.
- 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). Pain occurred in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than sickle cell disease. Pain lasted at least 2-4 hours and required parenteral narcotic treatment, or an equianalgesic dose of oral narcotics or parenteral non-steroidal anti-inflammatory drugs. These painful events may have been treated in any setting; however, the events, including events that were managed at home, will be considered for eligibility only if there is documentation of the event in a clinical record that may be reviewed by the investigator.
- Abnormal Transcranial Doppler Ultrasound (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. An infarct-like lesion is defined as an MRI signal abnormality that is at least 3 mm in one dimension and that is visible in two planes on fluid-attenuated inversion recovery (FLAIR) T2- weighted images, as determined by a neuroradiologist.
- Adequate organ function: renal, liver, cardiac, pulmonary function as defined by the protocol
- Adequate performance status (>50%) as defined by the protocol
- Liver/Iron Overload
- Note: Liver biopsy is optional to assess for iron overload in chronically transfused patients.
OR for Cohort #2 ONLY: Patient must be between 21 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.
- Provide Informed Consent
Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must voluntarily sign an informed consent form before any study procedures can occur.
- Patients (with sickle cell disease or beta thalassemia) must meet ……
- Age cohorts are now: 6 months – 17.99 years (Cohort 1) and 18-34.99 years (Cohort 2)
- Inclusion – sickle cell disease complications
Minimum of one episode of acute chest syndrome…
Recurrent painful events…. Remove “These painful events may have been treated in any setting; however, the events, including events that were managed at home, will be considered for eligibility only if there is documentation of the event in a clinical record that may be reviewed by the investigator.”
Abnormal TCD study – unchanged
At least one silent infarct lesion – unchanged
Additional high risk criteria related to sickle cell nephropathy, splenic sequestration, aplastic crisis, avascular necrosis, leg
ulcerations, recurrent priapism or infant dactylitis may be eligible.
Exclusion
In order to qualify for this clinical trial, the patient must not:
- Be receiving concomitant systemic anticoagulants and/or fibrinolytic therapies.
- Have a previously known hypersensitivity reaction to defibrotide.
- Be a female who is pregnant or breast-feeding
- Have documented uncontrolled infection at the time of study entry
- Have an unaffected fully HLA matched family donor willing to donate
- Have a performance score less than 50%
- Have demonstrated lack of compliance with medical care.
- Have clinically significant fibrosis or cirrhosis of the liver
- Have previously received a transplant
- Have contraindications to the use of defibrotide
Family Donor Eligibility Criteria
- The family donor must be a first generation relative, who is at least 18 years old, and match at least 3 out of 6 of the patient's HLA antigens.
- The family donor will be screened for SCD and those who are positive for Sickle Cell Disease or Sickle Cell/Beta Thalassemia
will not be able to donate - Maternal donors (mothers) are preferred over paternal (fathers) or sibling donors (≥18 yrs).
- The family donor will be screened for the following infectious disease: HIV, Hepatitis B, Hepatitis C, CMV, Syphilis, West Nile Virus, and Human T-lymphotropic Virus
- The family donor must have adequate blood cell function including red blood cells, white blood cells, and platelets
- The family donor must have a performance score of at least 80%.