NCT02836925

Brief Summary

This is a non-randomized, a single arm, phase II multicentre study of sofosbuvir plus ledipasvir (genotype 1 and 4) or sofosbuvir plus velpatasvir (genotype 2 and 3) for patients with hepatitis C virus-associated indolent B-cell lymphomas (HCV-RNA positive).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2016

Longer than P75 for phase_2

Geographic Reach
1 country

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 25, 2016

Completed
5 days until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
5 months until next milestone

First Posted

Study publicly available on registry

July 19, 2016

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2020

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

March 31, 2023

Status Verified

March 1, 2023

Enrollment Period

3.9 years

First QC Date

February 25, 2016

Last Update Submit

March 30, 2023

Conditions

Indolent B-cell LymphomaHepatitis C

Keywords

hepatitis CNHLIndolent B-cell lymphoma

Outcome Measures

Primary Outcomes (1)

  • SVR12

    Sustained virologic response (SVR12) defined as undetectability of HCV-RNA 12 weeks after completion of antiviral therapy

    12 weeks from the end of the treatment

Secondary Outcomes (9)

  • ORR

    12 weeks from the end of treatment

  • PFS

    36 months

  • EFS

    36 months

  • OS

    36 months

  • ORR for lymphoma

    12 weeks from the end of treatment

  • +4 more secondary outcomes

Study Arms (1)

Ledipasvir+Sofosbuvir,Sofosbuvir+Velpatasvir

EXPERIMENTAL

The study includes an antiviral treatment with interferon-free regimen followed by lymphoma restaging; following the end of antiviral treatment patients will be evaluated for sustained virological response and safety parameters every 3 months for 1 year and then every 6 months for 2 years. ORR and vital status will be also evaluated

Drug: Ledipasvir+SofosbuvirDrug: Sofosbuvir+Velpatasvir

Interventions

Ledipasvir+SofosbuvirDRUG

Patients with genotype 1 or genotype 4 Ledipasvir 90 mg + Sofosbuvir 400 mg * 12 weeks in previously untreated infected patients * 24 weeks for previously treated patients with uncertain subsequent retreatment options

Also known as: Harvoni
Ledipasvir+Sofosbuvir,Sofosbuvir+Velpatasvir
Sofosbuvir+VelpatasvirDRUG

Patients with genotype 2 or genotype 3 Sofosbuvir 400 mg + Velpatasvir 100 mg · 12 weeks of treatment

Also known as: Epclusa
Ledipasvir+Sofosbuvir,Sofosbuvir+Velpatasvir

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \>18 years
  • Indolent B cell lymphoma including: marginal zone lymphoma (nodal, extranodal, splenic and disseminated), lymphoplasmacytic lymphoma, small lymphocytic lymphoma, follicular lymphoma grade 1 and 2, CD5-negative B-cell lymphoma NOS
  • HCV-RNA positivity
  • Assessable HCV genotype
  • No previous therapy for the lymphoma
  • Measurable disease after diagnostic biopsy (longest axis ≥1.5 cm for nodal and ≥1 cm for extranodal lesions) and/or evaluable disease (quantifiable BM infiltrate and ≥5 x 109/l clonal B-cell in peripheral blood in case of exclusive BM/leukemic disease in CD5-negative Bcell lymphoma NOS)
  • No need of immediate lymphoma treatment defined as absence of all the following criteria: systemic symptoms, bulky nodal or extranodal mass (\>7 cm), symptomatic splenomegaly, progressive leukemic phase, serous effusions
  • Performance status \<2 according to ECOG scale
  • Adequate hematological counts: ANC \>1 x 109/L, hemoglobin \>9 g/dl (transfusion independent), platelet count \> 50 x 109/L (transfusion independent)
  • No central nervous system (CNS) disease (meningeal and/or brain involvement by lymphoma)
  • Adequate kidney function (creatinine clearance ≥ 45 ml/min)
  • Cardiac ejection fraction ≥45% (echocardiography or MUGA scan)
  • Normal lung function
  • Non peripheral neuropathy or active neurological non neoplastic disease of CNS
  • Non major surgical intervention prior 3 months to enrolment if not due to lymphoma and/or no other disease life-threatening that can compromise chemotherapy treatment
  • +11 more criteria

You may not qualify if:

  • Diagnosis of lymphoblastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma grade 3, primary mediastinal B-cell lymphoma
  • Previous anti-HCV treatment with sustained virological response
  • Diagnosis of cirrhosis (histological or Stiffness \>12 KpA)
  • CNS disease (meningeal and/or brain involvement by lymphoma)
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
  • Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug)
  • Concomitant therapy with amiodarone
  • Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina,
  • Cardiac ejection fraction \<45% (MUGA scan or echocardiography).
  • Creatinine clearance \<45 ml/min
  • Presence of major neurological disorders
  • HIV positivity, HBV positivity (HbsAg+ or HBV-DNA+) with the exception of HBcAb+, HbsAg-, HBsAb+/- patients with HBV-DNA negativity
  • Ongoing systemic bacterial, fungal or viral infections at the time of initiation of study treatment (defined as requiring therapeutic dosing of an antimicrobial, antifungal or antiviral agent)
  • Major surgical intervention prior 3 months to enrollment if not due to lymphoma and/or other
  • Prior malignancies other than lymphoma in the last 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

A.O. Spedali Civili

Brescia, BS, 25100, Italy

Location

Irccs Centro Di Riferimento Oncologico (Cro)

Aviano, Pordenone, 33801, Italy

Location

Ospedale San Bortolo

Vicenza, VI, 36100, Italy

Location

Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori

Milan, Italy

Location

Ospedale San Raffaele Ematologia

Milan, Italy

Location

U.O. Ematologia AO di Padova

Padua, Italy

Location

A.O. Universitaria Di Parma

Parma, 43126, Italy

Location

Ematologia Policlinico San Matteo

Pavia, 27100, Italy

Location

Ospedale Civile Piacenza

Piacenza, Italy

Location

Ematologia - Policlinico Umberto I Università Sapienza

Roma, Italy

Location

Dipartimento di Oncologia Medica ed Ematologia, Istituto Humanitas

Rozzano, Italy

Location

AOU Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, Italy

Location

Related Publications (1)

  • Merli M, Rattotti S, Spina M, Re F, Motta M, Piazza F, Orsucci L, Ferreri AJM, Perbellini O, Dodero A, Vallisa D, Pulsoni A, Santoro A, Sacchi P, Zuccaro V, Chimienti E, Russo F, Visco C, Zignego AL, Marcheselli L, Passamonti F, Luminari S, Paulli M, Bruno R, Arcaini L; Fondazione Italiana Linfomi. Direct-Acting Antivirals as Primary Treatment for Hepatitis C Virus-Associated Indolent Non-Hodgkin Lymphomas: The BArT Study of the Fondazione Italiana Linfomi. J Clin Oncol. 2022 Dec 10;40(35):4060-4070. doi: 10.1200/JCO.22.00668. Epub 2022 Jun 17.

    PMID: 35714311DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

ledipasvir, sofosbuvir drug combinationsofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Study Officials

  • Luca Arcaini

    Fondazione IRCCS Policlinico San Matteo di Pavia

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

February 25, 2016

First Posted

July 19, 2016

Study Start

March 1, 2016

Primary Completion

February 1, 2020

Study Completion

November 1, 2022

Last Updated

March 31, 2023

Record last verified: 2023-03

Locations

IT(13)