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

Fondazione Italiana Linfomi - ETS

Status and phase

Completed

Phase 2

Conditions

Indolent B-cell Lymphoma

Hepatitis C

Treatments

Drug: Ledipasvir+Sofosbuvir

Drug: Sofosbuvir+Velpatasvir

Study type

Interventional

Funder types

Other

Identifiers

NCT02836925

FIL_BArT

Details and patient eligibility

About

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).

Full 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.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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
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.

Exclusion criteria

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
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.