Chronic lymphocytic leukemia is a neoplasm of the lymphatic system characterized by an accumulation of B lymphocytes in peripheral blood, bone marrow and lymphatic organs. Diffuse Large Cell B Lymphoma is the most common subtype of non-Hodgkin's lymphoma, an aggressive tumor with rapid growth. Hepatitis B is an infectious disease, caused by the HBV virus, which causes acute or chronic inflammation of the liver, with consequent damage or destruction of hepatocytes. MedDRA version: 22.1 Level: PT
Conditions
Interventions
Trade Name: Vemlidy 25 mg compresse rivestite con film.
Product Name: Tenofovir Alafenamide (TAF)
Product Code: [NA]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tenofovir Alafenamide
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent according to ICH/EU/GCP and national local laws. 2) Male/non-pregnant/non-lactating female subjects >18 years old with newly diagnosed DLBCL/Chronic Lymphoid Leukemia who are going to receive treatment with rituximab in combination with chemotherapy. Female patients of childbearing potential and non-sterile male patients must practice two reliable methods of birth control with partner(s) beginning with initial treatment administration and continuing to 12 months after the last dose of study drug. Male patients must agree to refrain from sperm donation, from initial treatment administration until 12 months after the last dose of study drug. 3) HBsAg positivity, serum HBV-DNA negative or positive (=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1) Hepatic insufficiency for any reason (e.g. decompensated liver disease and with a Child Pugh Turcotte (CPT) score > 9 (i.e. class C). 2) History of other liver diseases such as hepatitis C, D, autoimmune hepatitis, primary biliary cirrhosis, Wilsons’ disease 3) Positive viral markers, such as IgM antibody to hepatitis A virus, hepatitis C virus, IgG antibody to hepatitis D virus, IgM antibody to hepatitis E virus, or antibody to HIV 4) Pregnant or breast-feeding women 5) Other major systemic disease, such as active infection, significant cardiac disease, neurological deficit or psychiatric disorder, that the investigators consider to be significant risk 6) Patients with moderate or severe renal failure satisfying one of the following conditions: - Glomerular filtration (GF) < 50 ml/min using the abbreviated MDRD: 186 × Creatinine (Cr) -1.154 × age -0.203 [Note: a multiplication factor of 0.742 for females and of 1.21 for patients of black race must be applied] - Creatinine clearance (CrCl) <50 ml/min according to the Cockcroft-Gault equation: (140-age in years) * (body weight [in kg]) 7) Intolerance to any of the components of the therapeutic regimen. Treatment with any investigational medicinal product (unapproved) in the last 30 days. 8) Any other disorder that, in the investigator's opinion, makes the patient ineligible for recruitment or that could interfere in his/her participation or in the conclusion of the study. 9) Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption. 10) Co-Administration of drugs interacting with TAF (please refer to Appendix C).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the incidence of HBV reactivation within the first 6 months treatment period in HBsAg positive patients with DLBCL /Chronic Lymphoid Leukemia treated with Rituximab, chemotherapy and TAF.;Secondary Objective: 1.To estimate the incidence of HBV reactivation during the 12-month treatment of TAF as a single agent 2.To estimate the incidence of HBV reactivation during the 12 months after TAF treatment 3.To estimate the incidence of HBV-related hepatitis or liver failure 4.To estimate the incidence of immune-chemotherapy delay due to HBV-reactivation 5.To estimate the overall survival 6.To estimate the progression free-survival 7.To evaluate the safety profile;Primary end point(s): Assessment of the percentage of patients presenting HBV reactivation within 6 months following the start of treatment with Rituximab, chemotherapy and TAF in in DLBCL and Chronic Lymphoid Leukemia patients.;Timepoint(s) of evaluation of this end point: Evaluation of the percentage of patients with a DNA level of HBV > 10 IU / ml at week 48, then within 6 months of starting treatment with Rituximab, chemotherapy and TAF. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Assessment of the percentage of patients presenting HBV reactivation during the 12-month treatment of TAF as a single agent in in DLBCL and Chronic Lymphoid Leukemia patients 2. Assessment of the percentage of patients presenting HBV reactivation during the 12 months after TAF treatment in DLBCL and Chronic Lymphoid Leukemia patients 3. Rate of patients stratified by DLBCL and Chronic Lymphoid Leukemia with hepatitis related to the HBV infection or with liver failure during their participation in the study 4. Assessment of chemotherapy delay due to HBV-reactivation in terms of percentage of patients with a delay of at least 7 days between chemotherapy cycles stratified by DLBCL and Chronic Lymphoid Leukemia. 5. Assessment of overall survival (OS) of the patients with DLBCL and with Chronic Lymphoid Leukemia 6. Assessment of progression free-survival (PFS) of the patients with DLBCL and with Chronic Lymphoid Leukemia 7. Safety assessment in order to estimate the incidence of adverse events and the percentage of patients who have to leave the study due to clinical adverse events or due to TAF-related laboratory abnormalities;Timepoint(s) of evaluation of this end point: During and after chemotherapy and during the 12 months of TAF monotherapy. | — |
Countries
Italy
Contacts
Public ContactCentro Dati GIMEMA
Fondazione GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Franco Mandelli ONLUS
Outcome results
None listed