Thrombotic Microangiopathies Clinical Trial
Official title:
A Pilot Trial of Using Pre-Transplant Risk Stratification and Prophylactic Defibrotide to Prevent Serious Thrombotic Microangiopathy in High-Risk Hematopoietic Stem Cell Transplant Patients
NCT number | NCT03384693 |
Other study ID # | 17-23356 |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | May 1, 2018 |
Est. completion date | July 31, 2020 |
Verified date | September 2021 |
Source | University of California, San Francisco |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 25 |
Est. completion date | July 31, 2020 |
Est. primary completion date | July 31, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 30 Years |
Eligibility | Inclusion Criteria 1. Age 0-30 years of age 2. Life expectancy > 6 months 3. Eastern Cooperative Oncology Group or Karnofsky Performance Status >40 4. Meets minimum organ function requirements per institutional standard of care guiding clearance for autologous or allogeneic stem cell transplantation. 5. 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: 1. >10 years of age 2. Non-Caucasian race/ Hispanic ethnicity 3. Undergoing haploidentical transplant 4. Minor ABO blood group mismatch Exclusion Criteria: 1. Age >30 years 2. Life expectancy < 6 months 3. Known bleeding diathesis or bleeding risk deemed by the treating physician to be a contraindication to administration of anticoagulants. 4. Known hypersensitivity reaction to defibrotide 5. Any patient not meeting TMA High-Risk criteria 6. Pregnant women are excluded from this study because they will be receiving teratogenic therapy as part of the stem cell transplant. |
Country | Name | City | State |
---|---|---|---|
United States | Benioff Children's Hospital at UCSF Medical Center | San Francisco | California |
Lead Sponsor | Collaborator |
---|---|
University of California, San Francisco |
United States,
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* Note: There are 17 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Incidence of Elevation of Single or Combination of Biomarkers Predictive of Development of TMA | Values will be analyzed to determine whether any one biomarker or a combination of biomarkers may be predictive of TMA development or severity. | 6 months post-transplant | |
Other | Incidence of TMA | Evidence of microangiopathy, with either clinical markers/organ dysfunction or presence of biomarkers, or one of the following: 1) presence of schistocytes in peripheral blood; 2) Histologic evidence of microangiopathy on a tissue specimen; 3) Undetectable haptoglobin with increased reticulocyte counts. If there is no evidence of microangiopathy but at least one clinical marker or at least 3 biomarkers, the participant will meet the criteria for TMA incidence. | Day 30, day 100 and day 180 post-transplant | |
Other | Non Relapse Mortality | Deaths which cannot be attributed to disease relapse or progression | Day 100 and day 180 post-transplant | |
Primary | Percent of Total Doses of Defibrotide That Were Missed [Feasibility] | Feasibility will be determined with regard to administration concurrently with chemotherapy and supportive medications before, during, and after stem cell infusion. | From first treatment with study drug to day +21 post Transplant | |
Primary | Participants With Reportable Serious Adverse Events [Safety] Per CTACAE v5 Grade 3 or Higher | Safety was assessed by evaluating drug-related Serious Adverse Events per CTACAE v5 that occur after prophylactic administration of defibrotide. Analyses will be performed for all patients having received at least one dose of study drug. | From first treatment with study drug to 6 months post-transplant | |
Primary | Participants With Clinically Significant Bleeding Requiring Discontinuation of Therapy [Safety] | Bleeding was assessed using Common Toxicity Criteria for Adverse Events version 4.03. (CTCAE). Study drug was permanently discontinued at grade 3 bleeding or higher. Analyses will be performed for all patients having received at least one dose of study drug. | From first treatment with study drug to 6 months post-transplant | |
Primary | Participants With Hypersensitivity Reaction Requiring Discontinuation of Therapy [Safety] | Hypersensitivity reaction will be assessed using Common Toxicity Criteria for Adverse Events version 4.03.
For grade 2 hypersensitivity reaction, study drug will be held until it resolves to grade 1 or lower. Study drug will be permanently discontinued at grade 3 hypersensitivity reaction or higher. Analyses will be performed for all patients having received at least one dose of study drug. |
From first treatment with study drug to 6 months post-transplant | |
Secondary | Number of Patients With TMA Enrolled on the Study | Evidence of microangiopathy, with either clinical markers/organ dysfunction or presence of biomarkers, or one of the following: 1) presence of schistocytes in peripheral blood; 2) Histologic evidence of microangiopathy on a tissue specimen; 3) Undetectable haptoglobin with increased reticulocyte counts. If there is no evidence of microangiopathy but at least one clinical marker or at least 3 biomarkers, the participant will meet the criteria for TMA incidence.
Based on prior analysis at our center, we anticipated an incidence of TA-TMA of 28.2% (95 CI, 17.8-38.6%) in the high-risk patients undergoing allogeneic transplants and 40% (95% CI, 13.9-69.5%) in the neuroblastoma patients undergoing planned tandem HSCT |
6 months post-transplant | |
Secondary | Number of Patients With Severe TMA | Severe TMA is defined as any TMA meeting the criteria in Objective 2 with the following complications: renal dysfunction requiring dialysis, pleural or pericardial effusion requiring any medical or surgical intervention, central nervous system dysfunction including seizure or posterior reversible encephalopathy syndrome, or death. | 6 months post-transplant |
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