Defibrotide TMA Prophylaxis Pilot Trial
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|ClinicalTrials.gov Identifier: NCT03384693|
Recruitment Status : Recruiting
First Posted : December 27, 2017
Last Update Posted : October 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Thrombotic Microangiopathies||Drug: Defibrotide||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Defibrotide 6.25mg/kg administered intravenously for 28-35 days|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 1, 2018|
|Estimated Primary Completion Date :||July 31, 2020|
|Estimated Study Completion Date :||July 31, 2021|
Experimental: Prophylactic Defibrotide
6.25mg/kg administered intravenously every 6 hours for 28 to 35 days, starting on the day before conditioning is initiated.
Defibrotide is an anticoagulant and fibrinolytic agent that has been shown to be an effective treatment in other endothelial disorders such as hepatic veno-occlusive disease.
Other Name: Defitelio
- Incidence of missed doses of defibrotide [feasibility] [ Time Frame: From first treatment with study drug to 6 months post-transplant ]Feasibility will be determined with regard to administration concurrently with chemotherapy and supportive medications before, during, and after stem cell infusion.
- Incidence of reportable Serious Adverse Events [safety] [ Time Frame: From first treatment with study drug to 6 months post-transplant ]Safety will be assessed by evaluating drug-related Serious Adverse Events that occur after prophylactic administration of defibrotide. Analyses will be performed for all patients having received at least one dose of study drug.
- Incidence of clinically significant bleeding requiring discontinuation of therapy [safety] [ Time Frame: From first treatment with study drug to 6 months post-transplant ]
Bleeding will be assessed using Common Toxicity for Adverse Events version 4.03.
For grade 2 bleeding, study drug will be held until it resolves to grade 1 or lower. Study drug will be permanently discontinued at grade 3 bleeding or higher. Analyses will be performed for all patients having received at least one dose of study drug.
- Incidence of hypersensitivity reaction requiring discontinuation of therapy [safety] [ Time Frame: From first treatment with study drug to 6 months post-transplant ]
Hypersensitivity reaction will be assessed using Common Toxicity 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.
- Incidence of TMA in patients enrolled on the study compared to historical controls. [ Time Frame: 6 months post-transplant ]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.
- Incidence of severe TMA [ Time Frame: 6 months post-transplant ]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.
- Incidence of elevation of single or combination of biomarkers predictive of development of TMA [ Time Frame: 6 months post-transplant ]Values will be analyzed to determine whether any one biomarker or a combination of biomarkers may be predictive of TMA development or severity.
- Incidence of TMA [ Time Frame: Day 30, day 100 and day 180 post-transplant ]TMA will defined as per the criteria listed under Outcome 2.
- Non relapse mortality [ Time Frame: Day 100 and day 180 post-transplant ]Deaths which cannot be attributed to disease relapse or progression
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03384693
|Contact: Christopher Dvorak, MD||415-476-2188||Christopher.Dvorak@ucsf.edu|
|Contact: Christine Higham, MD||415-476-2188||Christine.Higham@ucsf.edu|
|United States, California|
|Benioff Children's Hospital at UCSF Medical Center||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Chris Dvorak, MD 415-476-2188 email@example.com|
|Principal Investigator: Chis Dvorak, MD|
|Principal Investigator:||Christopher Dvorak, MD||University of California, San Francisco|