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Indolent B-cell LymphomaPhase 2NCT02836925

Ledipasvir+Sofosbuvir and Sofosbuvir+Velpatasvir for Pts With Indolent Bcell Lymphoma Associated With HCV Infection

A Phase 2 study testing Ledipasvir+Sofosbuvir and Sofosbuvir+Velpatasvir in people with Indolent B-cell Lymphoma and Hepatitis C, run by Fondazione Italiana Linfomi - ETS at 13 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Indolent B-cell Lymphoma, Hepatitis C
What is being tested?
Ledipasvir+Sofosbuvir and Sofosbuvir+Velpatasvir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
13 sitesItaly
Study dates
Mar 2016to Nov 2022
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Disease free of prior malignancies other than lymphoma for >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
  • Life expectancy > 6 months
  • No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
  • Written informed consent
  • Women must be:
  • postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)
  • surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
  • completely abstinent (at the discretion of the investigator/per local regulations) (periodic abstinence from intercourse is not permitted) or
  • if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg: condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 6 months after terminating treatment.
  • Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening
  • Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 1 month after receiving the last dose of study drug if not taking ribavirin of for 6 months after receiving the last dose of study drug if taking ribavirin.

Who cannot join

  • 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)
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  • 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
  • Life expectancy <6 months
  • Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
  • If female, the patient is pregnant or breast-feeding.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Italy13 sites

  • Irccs Centro Di Riferimento Oncologico (Cro)

    Aviano, Pordenone, 33801

  • A.O. Spedali Civili

    Brescia, BS, 25100

  • Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori

    Milan

  • Ospedale San Raffaele Ematologia

    Milan

  • U.O. Ematologia AO di Padova

    Padova

  • A.O. Universitaria Di Parma

    Parma, 43126

  • Ematologia Policlinico San Matteo

    Pavia, 27100

  • Ospedale Civile Piacenza

    Piacenza

  • Ematologia - Policlinico Umberto I Università Sapienza

    Roma

  • Dipartimento di Oncologia Medica ed Ematologia, Istituto Humanitas

    Rozzano

  • AOU Città della Salute e della Scienza di Torino

    Torino, 10126

  • Ospedale di Circolo e Fondazione Macchi

    Varese

  • Ospedale San Bortolo

    Vicenza, VI, 36100

Other trials in Italy

About this study

Official title: A Multicenter Study to Evaluate the Anti-viral Activity of an Interferon-free Treatment With Ledipasvir/Sofosbuvir (G1 and G4) and Sofosbuvir/Velpatasvir (G2 and G3) for Patients With Hepatitis C Virus-associated Indolent B-cell Lymphomas

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).

Read the detailed description

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.

Being tested
Ledipasvir+Sofosbuvir, Sofosbuvir+Velpatasvir
Keywords
hepatitis C, NHL, Indolent B-cell lymphoma
Medical subject headings
Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ledipasvir+SofosbuvirDrug

    Also called Harvoni

    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

  • Sofosbuvir+VelpatasvirDrug

    Also called Epclusa

    Patients with genotype 2 or genotype 3 Sofosbuvir 400 mg + Velpatasvir 100 mg

    • 12 weeks of treatment
Study groups in NCT02836925
Study groupRoleWhat they receive
Ledipasvir+Sofosbuvir,Sofosbuvir+VelpatasvirExperimentalThe 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
Receives: Drug: Ledipasvir+Sofosbuvir; Drug: Sofosbuvir+Velpatasvir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. SVR12

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

    Measured: 12 weeks from the end of the treatment

Secondary outcomes (9)

  1. ORR

    Overall response rate (ORR) of lymphoma: CR is defined by the complete disappearance of all detectable sites and symptoms; PR is defined as a more than 50% reduction. Responses different from CR/PR are defined as stable disease (SD); progressive disease (PD) is considered an increase in size of more than 50% of previously documented disease or the appearance of new lesions. Lymphoma response will be assessed 12 weeks after the end of antiviral treatment

    Measured: 12 weeks from the end of treatment

  2. PFS

    Progression-free survival (PFS) defined as the time between enrolment and progression or relapse or death from any cause.

    Measured: 36 months

  3. EFS

    Event-free survival (EFS) defined as time between enrolment and failure of treatment or death as a result of any cause

    Measured: 36 months

  4. OS

    Overall survival (OS) defined as the time between enrolment and death from any cause

    Measured: 36 months

  5. ORR for lymphoma

    ORR for lymphoma according to Matutes criteria (Matutes et al, Leukemia 2008) only in patients with splenic-marginal zone lymphoma (SMZL)

    Measured: 12 weeks from the end of treatment

  6. Rapid virological response

    rapid virologic response (RVR)

    Measured: 4 weeks

  7. Extended rapid virological response

    extended RVR (eRVR)

    Measured: 4 weeks

  8. Early virological response

    early virologic response (EVR)

    Measured: 4 weeks

  9. Toxicity - Incidence of Adverse Events

    toxicity will be classified according to definitions of Common Terminology Criteria for Adverse Event version 4.03 (CTCAE). It will be determined by the incidence of severe, life-threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2016 (estimated)
  2. Study startMar 2016
  3. Primary completionFeb 2020
  4. Study completionNov 2022

Resources

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
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02836925
Sponsor's protocol ID
FIL_BArT
Status last verified
Mar 2023
First submitted
25 Feb 2016
Last updated
31 Mar 2023
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 35714311

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ledipasvir+Sofosbuvir and Sofosbuvir+Velpatasvir in people with Indolent B-cell Lymphoma and Hepatitis C, run by Fondazione Italiana Linfomi - ETS at 13 sites in Italy.

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 18 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: finished, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Italy. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

SVR12 (time frame: 12 weeks from the end of the treatment). 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 NCT02836925, which also lists 1 linked publication.

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 31 Mar 2023.

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