Oral Hepatitis C Treatment for Indolent Lymphoma (OPTImaL) Study
Oral Hepatitis C Treatment for Indolent Lymphoma (OPTImaL) Study
There still remains the question if hepatitis C eradication with all oral therapy will lead
to a regression or cure of the low grade lymphoma. Thus, the hypothesis of this study is
that oral HCV therapy will lead to a high rate of hepatitis C eradication which will
correlate with a reduction of the size and extent of low-grade lymphoma. The hypothesis of
this study is that subjects with hepatitis C,regardless of genotype, who have low grade
lymphoma, when treated for hepatitis C without pegylated interferon will have a regression
of low grade non-Hodgkin's lymphoma. In this pilot study we will evaluate the effect of
Sofosbuvir/ledipasvir or sofosbuvir/ribavirin based antiviral therapy on the course of a
subset of HCV-related low grade B cell non-Hodgkin's lymphoma
Primary Objective This study will assess the safety, as measured by adverse events, in
subjects receiving hepatitis C treatment.
Secondary Objective The secondary objective of this study is to assess the rate of overall
response of B cell non-Hodgkin's lymphoma defined as either as partial response or complete
response according to revised international working group criteria for non-Hodgkin lymphoma.
Primary Endpoint Safety and tolerability of sofosbuvir/ledipasvir or sofosbuvir/ribavirin in
subjects with B-cell non-Hodgkin's lymphoma will be assessed by number of adverse events and
serious adverse events. In addition, the study will assess the number of subjects who had to
stop treatment due to adverse events or serious adverse events. The study will also examine
the number of subjects in which treatment for lymphoma had to be given due to clinical
Secondary Endpoints The secondary endpoint(s) of this study is to (1) Assess the rate of
overall response of B-cell Non-Hodgkin's lymphoma defined as either as partial response or
complete response according to revised international working group criteria for non-Hodgkin
lymphoma. (2) Determine the rate of sustained viral response in subjects with low-grade
Methods and Study Design
The study will plans to enroll approximately 21 subjects over the next 6-12 months for this
Subjects with low grade lymphoma with confirmed diagnosis of hepatitis C with a viral load >
1000 will be included in this study. Subjects may be treatment naïve or experienced to
hepatitis C therapy, however subjects must be treatment naïve to non-Hodgkin's lymphoma
treatment to be included in this study. All subjects will undergo staging studies at the
time of study screening which will include a whole body scans and a bone marrow biopsy. In
those with a prior bone marrow biopsy, those who had bone marrow involvement and biopsy was
<3 months from screening, then an additional biopsy is not needed. If bone marrow biopsy did
not show bone marrow involvement, a repeat bone marrow biopsy is needed at screening. If
complete data is not available from a prior biopsy, a repeat bone marrow biopsy will need to
be done. In addition, patients will have staging of liver disease by serologic markers of
liver inflammation, such as aspartate aminotransferase (AST) to platelet ratio (APRI) and
FibroTest® or (Fibro Sure®) or FibroScan®. If these methods are inconclusive, then a liver
biopsy may be obtained to determine if the patient has cirrhosis. Patients will be treated
regardless of stage of fibrosis. The rationale for examining cirrhosis is that these
patients may not respond as well and will require further surveillance for hepatocellular
cancer every 6 months. Additionally, hepatitis C viral load and genotype will be determined
prior to initiation of hepatitis C treatment.
This will be a multi- center study conducted at University of Texas Southwestern Medical
Center, Cornell Medical Center, and Memorial Sloan Kettering Cancer Center. Each site would
be expected to enroll 7 subjects in 6-12 months.
Treatment Naïve, with or without cirrhosis: sofosbuvir/ledipasvir one pill once a day for 12
Treatment experienced, with cirrhosis: sofosbuvir/ledipasvir one pill once a day with
weight-based ribavirin for 12 weeks. Weight-based ribavirin refers to use 1200 mg of
ribavirin in divided doses for those ≥75 kg and 1000 mg in divided dose for those <75kg.
Treatment experienced with cirrhosis : sofosbuvir/ledipasvir one pill once a day for 24
weeks. This option is for subjects who are unable to take ribavirin.
Treatment naïve or experienced without cirrhosis: sofosbuvir 400mg once daily and ribavirin
1000/1200 mg weight-based dosing in divided dose twice a day for 12 weeks.Treatment naïve or
experienced with cirrhosis: sofosbuvir 400 mg and weight-based ribavirin for 16 weeks
Treatment naïve, non-cirrhotic: sofosbuvir/ledipasvir fixed dose combination combined with
weight-based ribavirin for 12 weeks or treatment naïve with cirrhosis: sofosbuvir 400 mg
daily with weight-based ribavirin for 24 weeks.
Treatment experienced with cirrhosis will be excluded as the best treatment for this
population would require pegylated interferon.
Treatment naïve with or without cirrhosis or treatment experienced without cirrhosis:
sofosbuvir/Ledipasvir fixed dose combination for 12 weeks.
Treatment experienced with cirrhosis: sofosbuvir/ledipasvir for 24 weeks.
hepatitis C, low-grade lymphoma
University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University
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