Liver DiseasePhase 4OptimalNCT02717949
Oral Hepatitis C Treatment for Indolent Lymphoma (OPTImaL) Study
A Phase 4 study testing sofosbuvir/ledipasvir, sofosbuvir and Ribavirin in people with Liver Disease, run by University of Texas Southwestern Medical Center at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Disease
- What is being tested?
- sofosbuvir/ledipasvir, sofosbuvir and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- 25 Feb 2016to 18 Jul 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent.
- Male or female >18 years of age
- Serum HCV RNA levels of >1,000 IU per milliliter or higher
- 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.
Show all 26Show fewer
- Chronic Hepatitis C based on the judgment of the investigator
- HCV genotype 1, 2, 3, 4
- 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.
- 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
- 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.
- Karnofsky performance status > 70%
- Creatinine clearance ≥60 mL/min, as calculated by Cockcroft-Gault equation
- If patient will need ribavirin in their regimen then the following inclusion:
- Hg >12 g/dL for male
- Hg >11 g/dL for female
- All women of child-bearing potential who take ribavirin will need to have a negative urine pregnancy test.
Who cannot join
- Life expectancy < 6 months
- Any HCV treatment which uses pegylated interferon
- HCV genotype 3 Treatment experienced with cirrhosis
- Co-infection with hepatitis B
- Prior chemotherapy for lymphoma
- Lymphomas of other histologies other than the ones listed in section 3.3 above
Show all 15Show fewer
- Follicular lymphoma with large cell transformation
- Decompensated liver disease in which pegylated interferon is contraindicated.
- Female who is pregnant or breast feeding and HCV treatment requires use of ribavirin.
- Solid organ transplant
- 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
- Known hypersensitivity to ledipasvir, sofosbuvir, or formulation excipients.
- On a prohibited medication which cannot be stopped during the duration of HCV treatment.
- Female subject who is pregnant or breastfeeding
- HIV-infection
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UT Southwestern Medical Center
Dallas, Texas, 75390
Cornell Medical Center
New York, New York, 10065
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this 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.
Read more
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 progression.
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 lymphoma.
Read the detailed description
Methods and Study Design
The study will plans to enroll approximately 21 subjects over the next 6-12 months for this study.
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.
Setting:
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
Genotype 1:
Treatment Naïve, with or without cirrhosis: sofosbuvir/ledipasvir one pill once a day for 12 weeks.
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.
- Conditions
- Liver Disease
- Being tested
- sofosbuvir/ledipasvir, sofosbuvir, Ribavirin
- Keywords
- hepatitis C, low-grade lymphoma
- Medical subject headings
- Liver Diseases, Hepatitis C, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sofosbuvir/ledipasvirDrug
Also called Harvoni
sofosbuvir ledipasvir fixed dose combination given once a day by mouth
sofosbuvirDrug
Also called sovaldi
sofosbuvir 400 mg given one a daily orally and weight-based ribavirin given twice a day orally
RibavirinDrug
Also called copegus, rebetol, ribasphere
ribavirin 1200 mg given orally in divided dose for those >75kg and 1000 mg in divided dose for those <75 kg.
| Study group | Role | What they receive |
|---|---|---|
| sofosbuvir/ledipasvir | Experimental | sofosbuvir and ledipasvir fixed dose combination given orally once a day for genotype 1 and 4. Receives: Drug: sofosbuvir/ledipasvir |
| sofosbuvir and ribavirin | Experimental | Sofosbuvir 400 mg given orally once a day with weight-base ribavirin of 1200 mg for those >75 kg and 1000 mg for those <75kg given in divided dose twice a day. This intervention is for genotype 2 and 3 Receives: Drug: sofosbuvir; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number Subjects Who Experience Adverse Events on HCV Treatment as Assessed by Division of AIDS (DAIDS) Adverse Event (AE) Grading Table Version 2.0.
number of subjects who experience treatment-related adverse event on HCV treatment as assessed by DAIDS AE Grading Table version 2.
Measured: from drug dispensation until post-treatment week 36
Secondary outcomes (1)
Number of Subjects Who Have a Change in Lymph Node Size From Baseline After HCV Treatment
Number of subjects who have a change in the size of lymph node size from baseline
Measured: from baseline to post-treament week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study start25 Feb 2016
- Primary completion5 Jun 2017
- Study completion18 Jul 2017
Why it stopped: failure to recruit
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mamta K. Jain, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02717949
- Sponsor's protocol ID
- 042015-086
- Acronym
- Optimal
- Status last verified
- Jan 2019
- First submitted
- 10 Nov 2015
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Forghieri F, Luppi M, Barozzi P, Maffei R, Potenza L, Narni F, Marasca R. Pathogenetic mechanisms of hepatitis C virus-induced B-cell lymphomagenesis. Clin Dev Immunol. 2012;2012:807351. doi: 10.1155/2012/807351. Epub 2012 Jul 11.
PubMed 22844326Peveling-Oberhag J, Arcaini L, Hansmann ML, Zeuzem S. Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management. J Hepatol. 2013 Jul;59(1):169-77. doi: 10.1016/j.jhep.2013.03.018. Epub 2013 Mar 27.
PubMed 23542089Arcaini L, Merli M, Volpetti S, Rattotti S, Gotti M, Zaja F. Indolent B-cell lymphomas associated with HCV infection: clinical and virological features and role of antiviral therapy. Clin Dev Immunol. 2012;2012:638185. doi: 10.1155/2012/638185. Epub 2012 Aug 26.
PubMed 22956970Kasama Y, Mizukami T, Kusunoki H, Peveling-Oberhag J, Nishito Y, Ozawa M, Kohara M, Mizuochi T, Tsukiyama-Kohara K. B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-kappaB signalling. PLoS One. 2014 Mar 20;9(3):e91373. doi: 10.1371/journal.pone.0091373. eCollection 2014.
PubMed 24651473Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V, Delmas B, Valensi F, Cacoub P, Brechot C, Varet B, Troussard X. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med. 2002 Jul 11;347(2):89-94. doi: 10.1056/NEJMoa013376.
PubMed 12110736Vallisa D, Bernuzzi P, Arcaini L, Sacchi S, Callea V, Marasca R, Lazzaro A, Trabacchi E, Anselmi E, Arcari AL, Moroni C, Berte R, Lazzarino M, Cavanna L. Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: a multicenter Italian experience. J Clin Oncol. 2005 Jan 20;23(3):468-73. doi: 10.1200/JCO.2005.06.008.
PubMed 15659492Arcaini L, Vallisa D, Rattotti S, Ferretti VV, Ferreri AJM, Bernuzzi P, Merli M, Varettoni M, Chiappella A, Ambrosetti A, Tucci A, Rusconi C, Visco C, Spina M, Cabras G, Luminari S, Tucci M, Musto P, Ladetto M, Merli F, Stelitano C, d'Arco A, Rigacci L, Levis A, Rossi D, Spedini P, Mancuso S, Marino D, Bruno R, Baldini L, Pulsoni A. Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi. Ann Oncol. 2014 Jul;25(7):1404-1410. doi: 10.1093/annonc/mdu166. Epub 2014 May 5.
PubMed 24799461Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Brau N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.
PubMed 24725239Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34-44. doi: 10.1056/NEJMoa1208953.
PubMed 23281974Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10.
PubMed 24720702Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5.
PubMed 24209977Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, Illeperuma A, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Weiland O, Reesink HW, Ferenci P, Hezode C, Esteban R; VALENCE Investigators. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014 May 22;370(21):1993-2001. doi: 10.1056/NEJMoa1316145. Epub 2014 May 4.
PubMed 24795201
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Hepatitis C Treatment for Indolent Lymphoma (OPTImaL) Study
- ClinicalTrials.gov ID
- NCT02717949
- Acronym / sponsor ID
- Optimal / 042015-086
- Conditions
- Liver Disease
- Keywords
- hepatitis C, low-grade lymphoma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: failure to recruit
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University
- Study start
- 25 Feb 2016 (actual)
- Primary completion
- 5 Jun 2017 (actual)
- Study completion
- 18 Jul 2017 (actual)
- First posted
- 24 Mar 2016 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 progression.
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 lymphoma.
Detailed description
Methods and Study Design
The study will plans to enroll approximately 21 subjects over the next 6-12 months for this study.
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.
Setting:
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
Genotype 1:
Treatment Naïve, with or without cirrhosis: sofosbuvir/ledipasvir one pill once a day for 12 weeks.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sofosbuvir/ledipasvir | Experimental | Drug: sofosbuvir/ledipasvirsofosbuvir and ledipasvir fixed dose combination given orally once a day for genotype 1 and 4. |
| sofosbuvir and ribavirin | Experimental | Drug: sofosbuvir, Drug: RibavirinSofosbuvir 400 mg given orally once a day with weight-base ribavirin of 1200 mg for those >75 kg and 1000 mg for those <75kg given in divided dose twice a day. This intervention is for genotype 2 and 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Willing and able to provide written informed consent.
- Male or female >18 years of age
- Serum HCV RNA levels of >1,000 IU per milliliter or higher
- HCV treatment experienced or naïve.
- Chronic Hepatitis C based on the judgment of the investigator
Key exclusion criteria (15 listed)
- Life expectancy < 6 months
- Any HCV treatment which uses pegylated interferon
- HCV genotype 3 Treatment experienced with cirrhosis
- Co-infection with hepatitis B
- Prior chemotherapy for lymphoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sofosbuvir/ledipasvirAlso: Harvonisofosbuvir ledipasvir fixed dose combination given once a day by mouth | Drug | sofosbuvir/ledipasvir |
| sofosbuvirAlso: sovaldisofosbuvir 400 mg given one a daily orally and weight-based ribavirin given twice a day orally | Drug | sofosbuvir and ribavirin |
| RibavirinAlso: copegus, rebetol, ribasphereribavirin 1200 mg given orally in divided dose for those >75kg and 1000 mg in divided dose for those <75 kg. | Drug | sofosbuvir and ribavirin |
Primary outcome
Number Subjects Who Experience Adverse Events on HCV Treatment as Assessed by Division of AIDS (DAIDS) Adverse Event (AE) Grading Table Version 2.0.
Time frame: from drug dispensation until post-treatment week 36
number of subjects who experience treatment-related adverse event on HCV treatment as assessed by DAIDS AE Grading Table version 2.
1 secondary outcome
Number of Subjects Who Have a Change in Lymph Node Size From Baseline After HCV Treatment
Time frame: from baseline to post-treament week 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22844326Forghieri F, Luppi M, Barozzi P, Maffei R, Potenza L, Narni F, Marasca R. Pathogenetic mechanisms of hepatitis C virus-induced B-cell lymphomagenesis. Clin Dev Immunol. 2012;2012:807351. doi: 10.1155/2012/807351. Epub 2012 Jul 11.
- Background: PubMed 23542089Peveling-Oberhag J, Arcaini L, Hansmann ML, Zeuzem S. Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management. J Hepatol. 2013 Jul;59(1):169-77. doi: 10.1016/j.jhep.2013.03.018. Epub 2013 Mar 27.
- Background: PubMed 22956970Arcaini L, Merli M, Volpetti S, Rattotti S, Gotti M, Zaja F. Indolent B-cell lymphomas associated with HCV infection: clinical and virological features and role of antiviral therapy. Clin Dev Immunol. 2012;2012:638185. doi: 10.1155/2012/638185. Epub 2012 Aug 26.
- Background: PubMed 24651473Kasama Y, Mizukami T, Kusunoki H, Peveling-Oberhag J, Nishito Y, Ozawa M, Kohara M, Mizuochi T, Tsukiyama-Kohara K. B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-kappaB signalling. PLoS One. 2014 Mar 20;9(3):e91373. doi: 10.1371/journal.pone.0091373. eCollection 2014.
- Background: PubMed 12110736Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V, Delmas B, Valensi F, Cacoub P, Brechot C, Varet B, Troussard X. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med. 2002 Jul 11;347(2):89-94. doi: 10.1056/NEJMoa013376.
- Background: PubMed 15659492Vallisa D, Bernuzzi P, Arcaini L, Sacchi S, Callea V, Marasca R, Lazzaro A, Trabacchi E, Anselmi E, Arcari AL, Moroni C, Berte R, Lazzarino M, Cavanna L. Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: a multicenter Italian experience. J Clin Oncol. 2005 Jan 20;23(3):468-73. doi: 10.1200/JCO.2005.06.008.
- Background: PubMed 24799461Arcaini L, Vallisa D, Rattotti S, Ferretti VV, Ferreri AJM, Bernuzzi P, Merli M, Varettoni M, Chiappella A, Ambrosetti A, Tucci A, Rusconi C, Visco C, Spina M, Cabras G, Luminari S, Tucci M, Musto P, Ladetto M, Merli F, Stelitano C, d'Arco A, Rigacci L, Levis A, Rossi D, Spedini P, Mancuso S, Marino D, Bruno R, Baldini L, Pulsoni A. Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi. Ann Oncol. 2014 Jul;25(7):1404-1410. doi: 10.1093/annonc/mdu166. Epub 2014 May 5.
- Background: PubMed 24725239Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Brau N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.
- Background: PubMed 23281974Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34-44. doi: 10.1056/NEJMoa1208953.
- Background: PubMed 24720702Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10.
- Background: PubMed 24209977Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5.
- Background: PubMed 24795201Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, Illeperuma A, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Weiland O, Reesink HW, Ferenci P, Hezode C, Esteban R; VALENCE Investigators. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014 May 22;370(21):1993-2001. doi: 10.1056/NEJMoa1316145. Epub 2014 May 4.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mamta K. Jain, MD principal investigator
University of Texas Southwestern Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sofosbuvir/ledipasvir, sofosbuvir and Ribavirin in people with Liver Disease, run by University of Texas Southwestern Medical Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number Subjects Who Experience Adverse Events on HCV Treatment as Assessed by Division of AIDS (DAIDS) Adverse Event (AE) Grading Table Version 2.0. (time frame: from drug dispensation until post-treatment week 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02717949, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.