Brief Summary
A study to evaluate the long-term risk of hepatic failure with TURALIO™ (pexidartinib) and the mechanism of liver injury based upon liver biopsy information among patients who received or are receiving TURALIO™ (pexidartinib) and experience hepatotoxicity.
Brief Title
A Long-term Study Evaluating Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment
Detailed Description
This FDA post-marketing requirement study will evaluate the long-term risk of hepatic failure with TURALIO™ (pexidartinib) and the mechanism of liver injury based upon liver biopsy information among patients who received or are receiving TURALIO™ (pexidartinib) for symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery, and who experience hepatotoxicity. A liver biopsy will be collected from enrolled patients for central laboratory analysis of macrophage and immune cell profiles to investigate possible mechanisms of the hepatotoxicity. Additionally, 4 blood samples will be collected to evaluate liver function, other relevant safety tests, peripheral immune cells, and for pharmacogenomic testing. Enrolled patients will be followed at least yearly for 10 years to assess long-term risk of hepatic failure.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
908-992-6400
Central Contact Email
CTRinfo@dsi.com
Completion Date
Completion Date Type
Estimated
Conditions
Hepatotoxicity
Tenosynovial Giant Cell Tumor
Eligibility Criteria
Inclusion Criteria:
* Adult participants with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery
* Age ≥18 years old
* Emergence of at least one of the following liver test abnormalities due to TURALIO™ (pexidartinib) exposure:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) \>2 × ULN
* Isolated TBIL \>2 × ULN (excluding patients with Gilbert's syndrome)
* Isolated AST or ALT \>10 × ULN
* Alkaline phosphatase (ALP) \>2 x ULN with gamma-glutamyl transferase (GGT) \>2 x ULN
* Consent to study procedures, long-term safety follow-up, and use of data from the TURALIO™ (pexidartinib) Risk Evaluation and Mitigation Strategy (REMS) program
Exclusion Criteria:
* Not applicable
* Adult participants with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery
* Age ≥18 years old
* Emergence of at least one of the following liver test abnormalities due to TURALIO™ (pexidartinib) exposure:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) \>2 × ULN
* Isolated TBIL \>2 × ULN (excluding patients with Gilbert's syndrome)
* Isolated AST or ALT \>10 × ULN
* Alkaline phosphatase (ALP) \>2 x ULN with gamma-glutamyl transferase (GGT) \>2 x ULN
* Consent to study procedures, long-term safety follow-up, and use of data from the TURALIO™ (pexidartinib) Risk Evaluation and Mitigation Strategy (REMS) program
Exclusion Criteria:
* Not applicable
Inclusion Criteria
Inclusion Criteria:
* Adult participants with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery
* Age ≥18 years old
* Emergence of at least one of the following liver test abnormalities due to TURALIO™ (pexidartinib) exposure:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) \>2 × ULN
* Isolated TBIL \>2 × ULN (excluding patients with Gilbert's syndrome)
* Isolated AST or ALT \>10 × ULN
* Alkaline phosphatase (ALP) \>2 x ULN with gamma-glutamyl transferase (GGT) \>2 x ULN
* Consent to study procedures, long-term safety follow-up, and use of data from the TURALIO™ (pexidartinib) Risk Evaluation and Mitigation Strategy (REMS) program
* Adult participants with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery
* Age ≥18 years old
* Emergence of at least one of the following liver test abnormalities due to TURALIO™ (pexidartinib) exposure:
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) \>2 × ULN
* Isolated TBIL \>2 × ULN (excluding patients with Gilbert's syndrome)
* Isolated AST or ALT \>10 × ULN
* Alkaline phosphatase (ALP) \>2 x ULN with gamma-glutamyl transferase (GGT) \>2 x ULN
* Consent to study procedures, long-term safety follow-up, and use of data from the TURALIO™ (pexidartinib) Risk Evaluation and Mitigation Strategy (REMS) program
Gender
All
Gender Based
false
Keywords
Hepatotoxicity
Tenosynovial Giant Cell Tumor
Pexidartinib
TURALIO™
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04635111
Org Class
Industry
Org Full Name
Daiichi Sankyo
Org Study Id
PL3397-A-U401
Overall Status
Recruiting
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Long-term Study to Further Evaluate the Risk of Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment
Primary Outcomes
Outcome Description
Hepatic failure is defined as severe liver injury with encephalopathy and impaired synthetic function (INR \>= 1.5) as well as liver transplant and hepatic-related death.
Outcome Measure
Frequency of Hepatic Failure After Discontinuation of TURALIO™ (pexidartinib)
Outcome Time Frame
Baseline up to 10 years
Secondary Outcomes
Outcome Description
Liver test abnormalities were defined as the following: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) with concurrent total bilirubin (TBIL) \>2 × ULN; Isolated TBIL \>2 × ULN (excluding patients with Gilbert's syndrome); Isolated AST or ALT \>10 × ULN; Alkaline phosphatase (ALP) \>2 x ULN with gamma-glutamyl transferase (GGT) \>2 x ULN.
Outcome Time Frame
Baseline up to 10 years
Outcome Measure
Number of Participants With Liver Test Abnormalities
Outcome Time Frame
Baseline up to 10 years
Outcome Measure
Number of Participants With A Liver Transplant
Outcome Time Frame
Baseline up to 10 years
Outcome Measure
Number of Participants Experiencing Death
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Study Population
Adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery, who experience moderate or severe hepatotoxicity due to TURALIO™ (pexidartinib).
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Luca Paoluzzi
Investigator Email
lpaoluzzi@montefiore.org
Investigator Phone
6470000000