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

NCT03261349 | Unknown Phase 2 FDA Drug

• 1 other identifier: 201612066MIPB
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief 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 (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..

Conditions

Indolent Lymphoma

Keywords

Follicular lymphoma; MALT lymphoma; Waldenström's macroglobulinemia; Hepatitis C virus

Outcome Measures

Primary Outcomes (1)

• The complete remission rate

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

  During the first-year, every 3 months to evaluate

Secondary Outcomes (5)

• The durability of complete remission (disease-free interval)

  Follow-up every 3 motnhs for 3 years

• The overall response rate

  During the first-year, every 3 months to evaluate

• The association between HCV RNA load and response of lymphoma.

  During the first-year, every 3 months to evaluate

• The toxicity of Harvoni®.

  3 months

• Potential biomarkers predicting the response of Harvoni®.

  3 years

Study Arms (1)

Anti-HCV (Ledipasvir and sofosbuvir)

EXPERIMENTAL

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

Drug: Ledipasvir and sofosbuvir

Interventions

Ledipasvir and sofosbuvir DRUG

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

Also known as: HARVONI®

Anti-HCV (Ledipasvir and sofosbuvir)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Evidence of active opportunistic infections.
• Liver cirrhosis B and C (Child-Pugh score)
• Known HIV infection.
• Pregnant or lactating status.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Hepatitis C

Interventions

ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Sung-Hsin Kuo, M.D.,Ph.D.

  Department of Oncology, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

+886-2323456; shkuo101@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: August 25, 2017
• Study Start: September 1, 2017
• Primary Completion: December 31, 2020
• Study Completion: August 15, 2021
• Last Updated: August 25, 2017

Record last verified: 2017-08