Phase 2
N=25
Defibrotide TMA Prophylaxis Pilot Trial
Thrombotic Microangiopathies
Bottom Line
View on ClinicalTrials.gov: NCT03384693 ↗Enrolled (actual)
25
Serious AEs
12.0%
Results posted
Sep 2021
Primary outcome: Primary: Percent of Total Doses of Defibrotide That Were Missed [Feasibility] — 0.7 percentage of missed doses
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Defibrotide (Drug)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- University of California, San Francisco
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent of Total Doses of Defibrotide That Were Missed [Feasibility] |
0.7 | — |
| PRIMARY Participants With Reportable Serious Adverse Events [Safety] Per CTACAE v5 Grade 3 or Higher |
3 | — |
| PRIMARY Participants With Clinically Significant Bleeding Requiring Discontinuation of Therapy [Safety] |
3 | — |
| PRIMARY Participants With Hypersensitivity Reaction Requiring Discontinuation of Therapy [Safety] |
3 | — |
| SECONDARY Number of Patients With TMA Enrolled on the Study |
1 | — |
| SECONDARY Number of Patients With Severe TMA |
— | — |
Summary
Thrombotic microangiopathy (TMA) is a common complication in the stem cell transplant population. Certain populations within the hematopoietic stem cell transplant (HSCT) population are at a higher risk than others. Defibrotide is an endothelial stabilizing agent which may prevent the endothelial damage that triggers TMA in HSCT patients. The feasibility, safety, and efficacy of defibrotide prophylaxis in a pediatric transplant population is unknown. Twenty five patients age 0 to 30 years receiving autologous or allogeneic hematopoeitic stem cell transplant who meet TMA high risk criteria will be enrolled. Patients will receive Defibrotide for 28-35 days starting before conditioning, and will be closely monitored for any adverse events up through 6 months post-transplant. The feasibility of administering defibrotide will be evaluated as well as incidence of TMA.
Eligibility Criteria
Inclusion Criteria
- Age 0-30 years of age
- Life expectancy > 6 months
- Eastern Cooperative Oncology Group or Karnofsky Performance Status >40
- Meets minimum organ function requirements per institutional standard of care guiding clearance for autologous or allogeneic stem cell transplantation.
- Patients must meet TMA High-Risk criteria 5A or 5B below:
5A. Patients undergoing tandem autologous transplant with thiotepa in one or more of the conditioning regimens
OR:
5B. . Patients with at least 3 of the following characteristics:
- >10 years of age
- Non-Caucasian race/ Hispanic ethnicity
- Undergoing haploidentical transplant
- Minor ABO blood group mismatch
Exclusion Criteria
- Age >30 years
- Life expectancy < 6 months
- Known bleeding diathesis or bleeding risk deemed by the treating physician to be a contraindication to administration of anticoagulants.
- Known hypersensitivity reaction to defibrotide
- Any patient not meeting TMA High-Risk criteria
- Pregnant women are excluded from this study because they will be receiving teratogenic therapy as part of the stem cell transplant.
Data sourced from ClinicalTrials.gov (NCT03384693). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.