Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Digestive System Diseases

Heart and Blood Diseases

Rare Diseases

Lymphoma

Hepatitis A

Hepatitis C

Hepatitis

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Virus Diseases

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Lymphosarcoma

Follicular Lymphoma

Marginal Zone Lymphoma

Indolent B Cell Lymphoma

All Drugs and Chemicals

Anti-Infective Agents

Hepatitis C Antibodies

Sofosbuvir

Antiviral Agents

Ledipasvir

Ledipasvir, sofosbuvir drug combination

Harvoni® (90 mg ledipasvir and 400 mg sofosbuvir) one tablet daily for 12 weeks

To assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas.

Ledipasvir and sofosbuvir

Sung-Hsin Kuo, M.D.,Ph.D.

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..

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.

New Direct-Acting Antiviral Agent, HARVONI® (ledipasvir/sofosbuvir)

Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma

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

The complete remission rate by using Harvoni® (ledipasvir and sofosbuvir) as the first-line line therapy.

Complete remission and partial remission rate

The assessment of toxicity during the first 3 months

National Taiwan University Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma	NCT03261349	Indolent Lympho...	Ledipasvir and ...	20 Years -	National Taiwan University Hospital
Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma	NCT03261349	Indolent Lympho...	Ledipasvir and ...	20 Years -	National Taiwan University Hospital

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