Sickle Cell Disease
Conditions
Keywords
stem cell transplantation, sickle cell disease, haploidentical, defibrotide, matched unrelated donor
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 or MUD 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.
Interventions
DRUGDefibrotide
defibrotide will be given prophylactically prior to AlloSCT to determine if it decreases the incidence of SOS in this high risk population, and determine that it is safe and feasible to give along with myeloimmunoablative therapy and allogeneic transplant.
Sponsors
New York Medical College
University of California, Los Angeles
Medical College of Wisconsin
Johns Hopkins University
Dana-Farber Cancer Institute
Children's Hospital Los Angeles
Children's Hospital Medical Center, Cincinnati
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 21 Years
Healthy volunteers
No
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 * 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 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. * 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 * Patients with documented uncontrolled infection at the time of study entry are not eligible. * Patients who have an unaffected HLA matched sibling 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Contacts
CONTACTMitchell S Cairo, MD
CONTACTErin Morris, RN
PRINCIPAL_INVESTIGATORMitchell Cairo, MD
New York Medical College
Outcome results
None listed