Indolent LymphomaPhase 2NCT03261349
Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma
A Phase 2 study testing Ledipasvir and sofosbuvir in people with Indolent Lymphoma, run by National Taiwan University Hospital.
Trial summary
We and other investigators have revealed an association between Hepatitis C virus (HCV) seropositivity and an increased risk of developing marginal zone B-cell lymphoma (MZ), lymphoplasmacytic lymphoma (LPL, also known as Waldenström's macroglobulinemia), follicular lymphoma (FL), and diffuse large B-cell lymphoma… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Indolent Lymphoma
- What is being tested?
- Ledipasvir and sofosbuvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2017to 15 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients older than 18 years with histologically proven diagnoses of indolent B-cell NHLs and with positive genotype 1 or 2 HCV (non-cirrhotic status) were eligible.
- Indolent B-cell NHLs includes:
- Low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type: known as MALT lymphoma.
- Splenic marginal zone lymphomas (SMZL)
- Waldenström's macroglobulinemia (WM, known as lymphoplasmacytic lymphoma) .
- Grade 1, 2 follicular lymphoma (FL). 3 Stage I to III (modified Ann Arbor stage), and non-life threatening IV lymphoma. 4 Patients had not previously been treated with chemotherapy or immunotherapy, were eligible. 5 Patients with clinical, echographical, or radiological suspicion of lymphoma lesions were eligible.
Who cannot join
- Evidence of histologic transformation to a high-grade lymphoma (such as grade 3 and 4 follicular lymphoma, and high-grade MALT lymphoma).
- Life-threatening disseminated lymphoma.
- Primary gastric lesions were not eligible.
- Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer.
- Evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry.
- Evidence of symptomatic central nervous system (CNS) disease.
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- Evidence of active opportunistic infections.
- Liver cirrhosis B and C (Child-Pugh score)
- Known HIV infection.
- Pregnant or lactating status.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Pilot Phase II Study of New Direct-Acting Antiviral Agent, HARVONI® (Ledipasvir/Sofosbuvir), for the Treatment of Genotype 1 or 2 HCV-Associated Indolent B-Cell Non- Hodgkin's Lymphoma
We and other investigators have revealed an association between Hepatitis C virus (HCV) seropositivity and an increased risk of developing marginal zone B-cell lymphoma (MZ), lymphoplasmacytic lymphoma (LPL, also known as Waldenström's macroglobulinemia), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). The sustained virologic response (SVR) to treatment with interferon or pegylated (Peg)IFN with ribavirin was closely associated with the regression of HCV-associated B-cell NHL (mainly MZL, and LPL).
Currently, the second-generation direct-acting antiviral agents (DAAs), such as sofosbuvir, have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. After the approval of DAA for HCV therapy, several recent anecdotal case reports showed that indolent low-grade B-cell NHLs regressed after HCV clearance by DAAs. It is noted that the time to complete remission of these lymphomas was around 20 to 24 weeks after starting DAAs. These findings indicate that DAAs can eradicate the trigger of lymphomagenesis by curing chronic HCV infection.
Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas..
Read the detailed description
Although several epidemiological studies, including our study have been demonstrated the link between HCV and B-cell non-Hodgkin's lymphoma (NHL), the direct evidence of the HCV-associated-NHL remains uncertain. Direct antiviral agents (DAA) have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. Whether DAA treatment can cure HCV-associated indolent B-cell NHL remains unclear? If yes, a direct evidence of HCV-associated lymphomagenesis will be approved. Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of HCV-associated indolent B-cell NHL.
In the translational part, we will assess the expression pattern of BAFF-related canonical and non-canonical NF-κB signaling molecules by immunohistochemical (IHC) staining, and t(11;18)(q21;q21), and t(14;18)(q32;q21) by fluorescence in situ hybridization (FISH) in pre-treatment tumors samples of patients in prospectively predicting the antiviral responsiveness of HCV-positive indolent B-cell NHLs. The serum cytokines and chemokines, IFN-gamma, TNF-alpha, IL-4, IL-5, IL-6, IL-13 and CXCL13, BAFF level, and HCV RNA load before and after DAA treatment in HCV-associated indolent B-cell NHLs will be examined. The genotype of the HLA class II, and cloning followed by sequences of the VH region of the immunoglobulin gene derived from pre-treatment tumor samples will be assessed.
- Conditions
- Indolent Lymphoma
- Being tested
- Ledipasvir and sofosbuvir
- Keywords
- Follicular lymphoma, MALT lymphoma, Waldenström's macroglobulinemia, Hepatitis C virus
- Medical subject headings
- Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ledipasvir and sofosbuvirDrug
Also called HARVONI®
To assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas.
| Study group | Role | What they receive |
|---|---|---|
| Anti-HCV (Ledipasvir and sofosbuvir) | Experimental | Harvoni® (90 mg ledipasvir and 400 mg sofosbuvir) one tablet daily for 12 weeks Receives: Drug: Ledipasvir and sofosbuvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The complete remission rate
The complete remission rate by using Harvoni® (ledipasvir and sofosbuvir) as the first-line line therapy.
Measured: During the first-year, every 3 months to evaluate
Secondary outcomes (5)
The durability of complete remission (disease-free interval)
The lymphoma-free
Measured: Follow-up every 3 motnhs for 3 years
The overall response rate
Complete remission and partial remission rate
Measured: During the first-year, every 3 months to evaluate
The association between HCV RNA load and response of lymphoma.
The assessment of HCV RNA load
Measured: During the first-year, every 3 months to evaluate
The toxicity of Harvoni®.
The assessment of toxicity during the first 3 months
Measured: 3 months
Potential biomarkers predicting the response of Harvoni®.
Translational study
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start1 Sep 2017 (estimated)
- Primary completion31 Dec 2020 (estimated)
- Study completion15 Aug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Indolent LymphomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- New Direct-Acting Antiviral Agent, HARVONI® (ledipasvir/sofosbuvir)
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sung-Hsin Kuo, M.D.,Ph.D., Principal investigator, Department of Oncology, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03261349
- Sponsor's protocol ID
- 201612066MIPB
- Status last verified
- Aug 2017
- First submitted
- 9 Aug 2017
- Last updated
- 25 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase II Study of New Direct-Acting Antiviral Agent, HARVONI® (Ledipasvir/Sofosbuvir), for the Treatment of Genotype 1 or 2 HCV-Associated Indolent B-Cell Non- Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT03261349
- Acronym / sponsor ID
- 201612066MIPB
- Conditions
- Indolent Lymphoma
- Keywords
- Follicular lymphoma, MALT lymphoma, Waldenström's macroglobulinemia, Hepatitis C virus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Sep 2017 (estimated)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 15 Aug 2021 (estimated)
- First posted
- 25 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We and other investigators have revealed an association between Hepatitis C virus (HCV) seropositivity and an increased risk of developing marginal zone B-cell lymphoma (MZ), lymphoplasmacytic lymphoma (LPL, also known as Waldenström's macroglobulinemia), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). The sustained virologic response (SVR) to treatment with interferon or pegylated (Peg)IFN with ribavirin was closely associated with the regression of HCV-associated B-cell NHL (mainly MZL, and LPL).
Currently, the second-generation direct-acting antiviral agents (DAAs), such as sofosbuvir, have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. After the approval of DAA for HCV therapy, several recent anecdotal case reports showed that indolent low-grade B-cell NHLs regressed after HCV clearance by DAAs. It is noted that the time to complete remission of these lymphomas was around 20 to 24 weeks after starting DAAs. These findings indicate that DAAs can eradicate the trigger of lymphomagenesis by curing chronic HCV infection.
Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas..
Detailed description
Although several epidemiological studies, including our study have been demonstrated the link between HCV and B-cell non-Hodgkin's lymphoma (NHL), the direct evidence of the HCV-associated-NHL remains uncertain. Direct antiviral agents (DAA) have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. Whether DAA treatment can cure HCV-associated indolent B-cell NHL remains unclear? If yes, a direct evidence of HCV-associated lymphomagenesis will be approved. Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of HCV-associated indolent B-cell NHL.
In the translational part, we will assess the expression pattern of BAFF-related canonical and non-canonical NF-κB signaling molecules by immunohistochemical (IHC) staining, and t(11;18)(q21;q21), and t(14;18)(q32;q21) by fluorescence in situ hybridization (FISH) in pre-treatment tumors samples of patients in prospectively predicting the antiviral responsiveness of HCV-positive indolent B-cell NHLs. The serum cytokines and chemokines, IFN-gamma, TNF-alpha, IL-4, IL-5, IL-6, IL-13 and CXCL13, BAFF level, and HCV RNA load before and after DAA treatment in HCV-associated indolent B-cell NHLs will be examined. The genotype of the HLA class II, and cloning followed by sequences of the VH region of the immunoglobulin gene derived from pre-treatment tumor samples will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- New Direct-Acting Antiviral Agent, HARVONI® (ledipasvir/sofosbuvir)
| Arm | Type | Receives |
|---|---|---|
| Anti-HCV (Ledipasvir and sofosbuvir) | Experimental | Drug: Ledipasvir and sofosbuvirHarvoni® (90 mg ledipasvir and 400 mg sofosbuvir) one tablet daily for 12 weeks |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients older than 18 years with histologically proven diagnoses of indolent B-cell NHLs and with positive genotype 1 or 2 HCV (non-cirrhotic status) were eligible.
- Indolent B-cell NHLs includes:
Key exclusion criteria (10 listed)
- Evidence of histologic transformation to a high-grade lymphoma (such as grade 3 and 4 follicular lymphoma, and high-grade MALT lymphoma).
- Life-threatening disseminated lymphoma.
- Primary gastric lesions were not eligible.
- Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer.
- Evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry.
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 |
|---|---|---|
| Ledipasvir and sofosbuvirAlso: HARVONI®To assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas. | Drug | Anti-HCV (Ledipasvir and sofosbuvir) |
Primary outcome
The complete remission rate
Time frame: During the first-year, every 3 months to evaluate
The complete remission rate by using Harvoni® (ledipasvir and sofosbuvir) as the first-line line therapy.
5 secondary outcomes
The durability of complete remission (disease-free interval)
Time frame: Follow-up every 3 motnhs for 3 years
The overall response rate
Time frame: During the first-year, every 3 months to evaluate
The association between HCV RNA load and response of lymphoma.
Time frame: During the first-year, every 3 months to evaluate
The toxicity of Harvoni®.
Time frame: 3 months
Potential biomarkers predicting the response of Harvoni®.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2017.
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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.
Sung-Hsin Kuo, M.D.,Ph.D. principal investigator
Department of Oncology, National Taiwan University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ledipasvir and sofosbuvir in people with Indolent Lymphoma, run by National Taiwan University Hospital.
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 6 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 25 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sung-Hsin Kuo, M.D.,Ph.D. (+886-2323456 ext. 67144, shkuo101@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The complete remission rate (time frame: During the first-year, every 3 months to evaluate). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Aug 2017.