We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease (NYMC-571)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02675959
Recruitment Status : Recruiting
First Posted : February 5, 2016
Last Update Posted : June 21, 2022
Sponsor:
Collaborators:
University of California, Los Angeles
Medical College of Wisconsin
Tufts Medical Center
Baylor College of Medicine
Johns Hopkins University
Dana-Farber Cancer Institute
Children's Hospital Los Angeles
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Tracking Information
First Submitted Date  ICMJE January 22, 2016
First Posted Date  ICMJE February 5, 2016
Last Update Posted Date June 21, 2022
Actual Study Start Date  ICMJE July 1, 2017
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • 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 [ Time Frame: 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. [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2016)
  • 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 [ Time Frame: 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 +30 or until discharge.
  • All patients will be monitored for the development of SOS. [ Time Frame: 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.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE Drug: Defibrotide
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.
Study Arms  ICMJE Experimental: Defibrotide prophylaxis
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).
Intervention: Drug: Defibrotide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 2, 2016)		 40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 34 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mitchell S Cairo, MD 914-594-2150 Mitchell_Cairo@nymc.edu
Contact: Erin Morris, RN 714-964-5359 erin_morris@nymc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02675959
Other Study ID Numbers  ICMJE NYMC 571
4090 ( Other Grant/Funding Number: OPD )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Mitchell Cairo, New York Medical College
Original Responsible Party Same as current
Current Study Sponsor  ICMJE New York Medical College
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • University of California, Los Angeles
  • Medical College of Wisconsin
  • Tufts Medical Center
  • Baylor College of Medicine
  • Johns Hopkins University
  • Dana-Farber Cancer Institute
  • Children's Hospital Los Angeles
Investigators  ICMJE
Principal Investigator: Mitchell Cairo, MD New York Medical College
PRS Account New York Medical College
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP