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

NCT ID: NCT02836925

Last Updated: 2023-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2022-11-30

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).

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.

Conditions

Indolent B-cell Lymphoma; Hepatitis C

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ledipasvir+Sofosbuvir,Sofosbuvir+Velpatasvir

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

Group Type: EXPERIMENTAL

Ledipasvir+Sofosbuvir

Intervention Type: DRUG

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+Velpatasvir

Intervention Type: DRUG

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

· 12 weeks of treatment

Interventions

Ledipasvir+Sofosbuvir

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

Intervention Type: DRUG

Sofosbuvir+Velpatasvir

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

· 12 weeks of treatment

Intervention Type: DRUG

Other Intervention Names

Harvoni; Epclusa

Eligibility Criteria

Inclusion Criteria

1. Age >18 years

2. 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

3. HCV-RNA positivity

4. Assessable HCV genotype

5. No previous therapy for the lymphoma

6. 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)

7. 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

8. Performance status <2 according to ECOG scale

9. Adequate hematological counts: ANC >1 x 109/L, hemoglobin >9 g/dl (transfusion independent), platelet count > 50 x 109/L (transfusion independent)

10. No central nervous system (CNS) disease (meningeal and/or brain involvement by lymphoma)

11. Adequate kidney function (creatinine clearance ≥ 45 ml/min)

12. Cardiac ejection fraction ≥45% (echocardiography or MUGA scan)

13. Normal lung function

14. Non peripheral neuropathy or active neurological non neoplastic disease of CNS

15. 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

16. 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

17. Life expectancy > 6 months

18. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent

19. Written informed consent

20. 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.

21. Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening

22. 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.

Exclusion Criteria

1. Diagnosis of lymphoblastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma grade 3, primary mediastinal B-cell lymphoma

2. Previous anti-HCV treatment with sustained virological response

3. Diagnosis of cirrhosis (histological or Stiffness >12 KpA)

4. CNS disease (meningeal and/or brain involvement by lymphoma)

5. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances

6. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug)

7. Concomitant therapy with amiodarone

8. 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,

9. Cardiac ejection fraction <45% (MUGA scan or echocardiography).

10. Creatinine clearance <45 ml/min

11. Presence of major neurological disorders

12. HIV positivity, HBV positivity (HbsAg+ or HBV-DNA+) with the exception of HBcAb+, HbsAg-, HBsAb+/- patients with HBV-DNA negativity

13. 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)

14. Major surgical intervention prior 3 months to enrollment if not due to lymphoma and/or other

15. 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

16. Life expectancy <6 months

17. Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.

18. If female, the patient is pregnant or breast-feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luca Arcaini

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Policlinico San Matteo di Pavia

Locations

A.O. Spedali Civili

Brescia, BS, Italy

Irccs Centro Di Riferimento Oncologico (Cro)

Aviano, Pordenone, Italy

Ospedale San Bortolo

Vicenza, VI, Italy

Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori

Milan, , Italy

Ospedale San Raffaele Ematologia

Milan, , Italy

U.O. Ematologia AO di Padova

Padua, , Italy

A.O. Universitaria Di Parma

Parma, , Italy

Ematologia Policlinico San Matteo

Pavia, , Italy

Ospedale Civile Piacenza

Piacenza, , Italy

Ematologia - Policlinico Umberto I Università Sapienza

Roma, , Italy

Dipartimento di Oncologia Medica ed Ematologia, Istituto Humanitas

Rozzano, , Italy

AOU Città della Salute e della Scienza di Torino

Torino, , Italy

Ospedale di Circolo e Fondazione Macchi

Varese, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 35714311 (View on PubMed)

Other Identifiers

FIL_BArT

Identifier Type: -

Identifier Source: org_study_id