Patients with relapsed/refractory BCL-2 positive peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and other nodal T-cell lymphomas of T-follicular helper origin (TFH) MedDRA version: 21.0 Level: PT Classification code 10042980 Term: T-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10042979 Term: T-cell lymphoma r
Conditions
Interventions
Trade Name: VENCLYXTO - 10 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PVC/PE/PCTFE-ALU) - 14 (7X2) COMPRESSE (DOSE UNITARIA)
Product Name: Venetoclax
Product Code: [IMP1]
Pharmaceutical
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Histologically documented diagnosis of BCL-2 positive PTCL-NOS, AITL, TFH as defined in the 2016 edition of the World Health Organization (WHO) classification. Only patients with percentage of BCL-2 positive tu-mor cells >= 25% in the relapse biopsy, if available, or otherwise in the ini-tial biopsy, will be included onto the study; • Age >= 18 years • Relapsed or refractory to at least one previous standard line of treatment • Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed). Note: Patients with only bone marrow involvement are eligible • Adequate hematological counts defined as follows: - Absolute Neutrophil count (ANC) > 1.0 x 10^9/L unless due to bone marrow involvement by lymphoma - Platelet count >= 50.000/mm^3 unless due to bone marrow involvement by lymphoma • Adequate renal function defined as follows: - Creatinine clearance >= 30 mL/min • Adequate hepatic function per local laboratory reference range as follows: - Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 months • 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 (periodic abstinence from intercourse is not permit-ted) or if sexually active, be practicing a highly effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method (e.g.: 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 con-trol measures for at least 1 month after terminating treatment. - women of childbearing potential must have a negative pregnancy test at screening • Men must agree to use an acceptable method of contraception (fort them-selves 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. Male even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: - practice effective barrier contraception during the entire study treatment period and through 1 months after the last dose of study drug, or - agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the femal
Exclusion criteria
Exclusion criteria: •Histological diagnosis different from BCL-2 positive PTCL-NOS, AITL, and TFH • Allogeneic or autologous stem cell transplant within 6 months prior to the informed consent signature • Treatment with any of the following within 7 days prior to the first dose of study drug: - steroid therapy for anti-neoplastic intent - moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Ap-pendix C for examples) - moderate or strong CYP3A inducers (see Appendix C for examples) • Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug • History of CNS involvement by lymphoma • Administration or consumption of any of the following within 3 days prior to the first dose of study drug: - grapefruit or grapefruit products - Seville oranges (including marmalade containing Seville oranges) - star fruit • Previous treatment with a BCL-2 family protein inhibitor • Subject is known to be positive for HIV (HIV testing is not required) • Cardiovascular disease (NYHA class >=2) • Creatinine Clearance 2000 UI/ml is criteria of exclusion - HBsAg negative but HBsAb positive - HBsAg negative but HBcAb positive - Patients HBsAg positive with HBV DNA < 2000 UI/ml and HBsAg nega-tive but HBcAb positive will be eligible for the study only if they accept to receive prophylactic Lamivudine 100 mg/daily for all the period of treat-ment and at least for 12 months after the end of therapy. Treatment with ABT-199 should be stopped in case of hepatitis reactivation. • Active HCV positive hepatitis • If female, the patient is pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ABT-199 in terms of overall response rate (ORR).;Secondary Objective: To assess the efficacy and safety of ABT-199 as measured by: - Complete response rate (CR); Partial response rate (PR); Stable Disease rate (SD); - Overall Survival (OS); - Time to response (TTR); - Duration of response (DoR); - Progression Free Survival (PFS); - Duration of Treatment; - Safety of ABT-199 in terms of relevant toxicity; - Safety of ABT-199 in terms of overall toxicity; Explorative objectives • To assess the relationship between response and level of BCL-2 expression;Primary end point(s): Overall response rate (ORR);Timepoint(s) of evaluation of this end point: After the first 3 cycles or, in case of discontinuation, at the EoT visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Complete remission (CR); Partial response (PR); Stable Desease (SD); Time To Response (TTR); Duration of Remission (DoR); Progression free Sruvival (PFS); Overall Survival (OS); Duration of treatment (DoT); Safety;Timepoint(s) of evaluation of this end point: After 3 cycles from the date of the first dose and at each restaging; After 3 cycles from the date of the first dose and at each restaging; After 3 cycles from the date of the first dose and at each restaging; 1 year from the date of the first dose; 6 months from the first response assesment; 1 year from the date of the first dose; 1 year from the date of the first dose; 1 year from the date of the first dose; Throughout all the active treatment period | — |
Countries
Italy
Contacts
Public ContactUffici Studi FIL - Area Start up
Fondazione Italiana Linfomi Onlus
Outcome results
None listed