Oral Hepatitis C Treatment for Indolent Lymphoma (OPTImaL) Study

Conditions:Lymphoma, Gastrointestinal, Hepatitis
Therapuetic Areas:Gastroenterology, Immunology / Infectious Diseases, Oncology
Age Range:18 - Any
Start Date:February 25, 2016
End Date:July 18, 2017

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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.


Genotype 1:

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.

Genotype 2:

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

Genotype 3:

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.

Genotype 4:

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.

Inclusion Criteria:

1. Willing and able to provide written informed consent.

2. Male or female >18 years of age

3. Serum HCV RNA levels of >1,000 IU per milliliter or higher

4. HCV treatment experienced or naïve.

- HCV treatment naïve: No prior exposure to any Interferon, ribavirin, or other
approved or experimental HCV-specific directly acting antivirals

- HCV Treatment-Experienced: Virologic failure after treatment with Pegylated
interferon + ribavirin, Non-structural 3/4a (NS3/4A) protease inhibitor plus
pegylated interferon + ribavirin, or regimen of sofosbuvir±ribavirin± pegylated
interferon regimen.

5. Chronic Hepatitis C based on the judgment of the investigator

6. HCV genotype 1, 2, 3, 4

7. If the patient is determined to be cirrhotic (based on criteria outlined earlier), the
patient must have an ultrasound done within 6 months prior to enrollment with no
evidence of hepatocellular carcinoma.

8. Indolent Non-Hodgkin's lymphoma , which may include the following :

- Nodal Marginal zone lymphoma

- Extranodal marginal zone lymphoma (MALT)

- Splenic marginal zone lymphoma

- Follicular lymphoma Grade 1-3a with low tumor burden*, FLIPI 2 risk category of
either low (i.e. no risk factors) or intermediate (1-2 risk factors), and with no
B symptoms. B symptoms are defined as:

- Fever (i.e., temperature >38°C [>100.4°F]) for 3 consecutive days

- Weight loss exceeding 10% of body weight in 6 months

- Drenching night sweats

- Lymphoplasmacytic lymphoma

9. No prior chemotherapy

- Low tumor burden is defined as normal lactate dehydrogenase, largest nodal or
extranodal mass less than 7 cm, up to three nodal sites containing nodes with a
diameter greater than 3 cm, no clinically significant serous effusions detectable
by physical examination or positron emission tomography (PET)/CT scan, and spleen
enlargement up to 16 cm by CT without any evidence of portal hypertension.

10. Karnofsky performance status > 70%

11. Creatinine clearance ≥60 mL/min, as calculated by Cockcroft-Gault equation

12. If patient will need ribavirin in their regimen then the following inclusion:

- Hg >12 g/dL for male

- Hg >11 g/dL for female

13. All women of child-bearing potential who take ribavirin will need to have a negative
urine pregnancy test.

Exclusion Criteria:

1. Life expectancy < 6 months

2. Any HCV treatment which uses pegylated interferon

3. HCV genotype 3 Treatment experienced with cirrhosis

4. Co-infection with hepatitis B

5. Prior chemotherapy for lymphoma

6. Lymphomas of other histologies other than the ones listed in section 3.3 above

7. Follicular lymphoma with large cell transformation

8. Decompensated liver disease in which pegylated interferon is contraindicated.

9. Female who is pregnant or breast feeding and HCV treatment requires use of ribavirin.

10. Solid organ transplant

11. Any interferon- containing agent within 8 weeks prior to screening or any prior
exposure to HCV-specific antivirals agent(s), other than NS3/ 4A protease inhibitor
and sofosbuvir

12. Known hypersensitivity to ledipasvir, sofosbuvir, or formulation excipients.

13. On a prohibited medication which cannot be stopped during the duration of HCV

14. Female subject who is pregnant or breastfeeding

15. HIV-infection
We found this trial at
2201 Inwood Rd
Dallas, Texas 75235
(214) 645-8300
Phone: 214-648-9914
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
Dallas, TX
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New York, New York 10021
Principal Investigator: Sonal Kumar, MD
Phone: 646-962-2085
New York, NY
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1275 York Ave
New York, New York 10021
(212) 639-2000
Principal Investigator: Maya Gambarin-Gewlan, MD
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
New York, NY
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