A Phase 4 interventional study of Ledipasvir 90mg/Sofosubvir 400mg in Hematopoietic Stem Cell Transplantation, sponsored by Kaiser Permanente. Withdrawn at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-31.
Sponsored by Kaiser Permanente · Phase 4, Interventional, and Treatment
The prevalence of Hepatitis C Virus (HCV) infection was reported to range between 10% and up to 30% prior to institution of routine HCV screening in recipients of HCT (hematopoietic cell transplantation). In an Italian prospective study 6% of HCT candidates were positive for HCV RNA. HCV in recipients of HCT carries both short-term and long-term consequences. In the short-term those with HCV after hematopoietic cell transplantation have been associated with risk for sinusoidal obstruction syndrome especially in patients with some level of hepatic dysfunction going in to the transplant. In addition, the type of conditioning chemotherapy (e.g., busulfan) and radiation may increase risk for sinusoidal obstruction syndrome. The rate of hematopoietic recovery was found to be lower in HCV infected recipients, with delayed neutrophil and platelet engraftment.
In the long-term, HCV may flare up once immunosuppression is being tapered off. The issue of reactivation of viral hepatitis (HBV and HCV) after HCT has been well documented. The risk for HCV reactivation in allogenic HCT in one study was reported at 100% by 12 months after HCT, with risk for death related to HCV of 8%. Also, of concern is rapid progression of liver disease in long-term survivors of HCV+ HCT. In such patients, cumulative incidence of cirrhosis has been reported in up to 11% and 24% at 15 and 20 years after HCT respectively.
Hepatitis C infection is associated with significant morbidity and mortality, due to the short-term and long-term complications associated with it. Treatment of hepatitis C virus with direct-acting antiviral (DAA) agents pre-hematopoietic cell transplantation (HCT) in candidates with hepatitis C may lead to reduction of both short-term and long-term complications from it.
Treatment with DAA's pre-HCT in candidates with hepatitis C would potentially prevent complications of hepatitis C infection; prevent reactivation of hepatitis C post-HCT, prevent delay in hematopoietic recovery (especially neutrophils and platelet), possibly reduce risk for sinsusoidal obstruction syndrome, prevent relapse of malignancy that could be related to hepatitis C (non-Hodgkin lymphoma), reduce non-relapse mortality and long-term complications (cirrhosis).
This is an open-label observational/ feasibility study to treat candidates for HCT infected with hepatitis C prior to the transplantation to reduce the complications associated with hepatitis C in the post-transplant setting.
The study will be conducted at Kaiser Permanente Los Angeles Medical Center and City of Hope National Medical Center, Duarte, CA.
There is no data available on the outcomes of treating hepatitis C with DAA's pre-HCT in candidates with hepatitis C infection. The ASBMT task force made recommendation to consider treating hepatitis C infection pre-HCT based on potential benefits it may be associated with. A single case report has documented benefit of treating a donor infected with hepatitis C prior to stem cell collection with DAA and ribavirin
Subject Population will include autologous or allogeneic HCT candidates (for hematologic malignancy) who have hepatitis C infection. Subjects will be considered treatment-experienced if they have received prior interferon-based therapy. Treatment-experienced patients with prior use of DAA(s) are excluded from study participation.
This study will treat HCV patients prior to HCT, with the goal of reducing early post HCT complications in the first 100 days post HCT followed by measuring outcomes at 2 years post HCT.
Subjects will receive LDV 90mg/SOF 400mg FDC for 12 weeks.
Female participant without childbearing potential must meet at least one of the following:
Female participant of childbearing potential must meet at least one of the following:
Participant must have the following indicator- of chronic hepatitis C virus infection prior to study enrollment:
Exclusion Criteria:
Screening laboratory analyses shows any of the following abnormal laboratory results:
Estimated Glomerular filtration (eGFR) rate \< 30 mL/min
Evidence of cirrhosis, documented by one of the following:
Liver biopsy histologic diagnosis: Metavir Score greater than 3 (includes 3 - 4 or ¾) or Ishak score greater than 4 In the absence of liver biopsy: a FibroScan score greater than or equal to 12.5 kPa or Fibrotest score of >0.75 AND an APRI score greater than 1.5
Ledipasvir 90mg/Sofosubvir 400mg fixed-dose combination (FDC) tablet for 12 weeks.
Drug: Ledipasvir 90mg/Sofosubvir 400mg
Ledipasvir 90mg/Sofosubvir 400mg (LDV/SOF) FDC is to be administered once daily with or without food for12 weeks.
Also known as: Harvoni
Safety and Tolerability of LDV/SOF Treatment in Candidates for HCT with hepatitis C infection
To assess the safety and tolerability/feasibility of the two agent combination, ledipasvir and sofosbuvir (LDV/SOF), through evaluation of toxicities, including type frequency, severity, attribution, time course and duration.
Time frame: 2 year
Rate of HCV Relapse Post HCT
To estimate the rate of hepatitis C relapse post HCT - until 2 year after HCT
Time frame: 2 Years
Effect of Virologic Suppression on Post HCT Complications
To evaluate the effect of virologic cure on the short term complications after HCT: hematopoietic recovery (neutrophil and platelet count), liver test abnormality, sinusoidal obstruction syndrome, liver disease decompensation in those with advanced fibrosis
Time frame: 2 Years
Proportion of Patients with Sustained Virologic Response at Time of Transplant
To estimate the proportion of patients who attained SVR by the time of transplantation (day 0 of HCT), and remain HCV negative at day 30, day 100, day 180, year 1 and year 2 post HCT
Time frame: 2 Years
Cumulative Incidence of HCV Relapse
To estimate the cumulative incidence of hepatitis C relapse
Time frame: 2 Years
Progression of Liver Fibrosis After Transplant
Monitoring for progression of liver fibrosis post-HCT compared to baseline (prior to initiation of DAA treatment)
Time frame: 2 years
Plan to share: Undecided
No publications or documents are linked to this record.
This study is withdrawn, as verified in Aug 2018. You cannot join it, but the record below documents what was studied.
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