A Phase II, Open Label, Multicenter Trial of Venetoclax (ABT-199/GDC-0199) as Single Agent in 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)

FIL_VERT

The FIL_VERT study is a phase II, open label, multicenter clinical trial. The primary of objective of the Study is to evaluate the efficacy of Venetoclax ABT-199/GDC-0199) in terms of overall response rate (ORR) in 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)

2018-09-25

2020-03-04

2023-02-17

Terminated

Early phase I

22

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 * At least one site of measurable nodal or extranodal disease at baseline ≥ 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) ≤ 3.0 x ULN * Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syn-drome or of non-hepatic origin) * Subject understands and voluntarily signs an informed consent form ap-proved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific pro-cedures * Subject must be able to adhere to the study visit schedule and other pro-tocol requirements * Subject must be able to swallow capsules or tablets * Life expectancy ≥ 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 per-mitted) or if sexually active, be practicing a highly effective method of birth control (e.g., prescription oral contraceptives, contraceptive injec-tions, 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, be-fore entry, and must agree to continue to use the same method of con-traception throughout the study. They must also be prepared to contin-ue birth control measures for at least 1 month after terminating treat-ment. * women of childbearing potential must have a negative pregnancy test at screening * Men must agree to use an acceptable method of contraception (fort 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. 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 \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female part-ner\] and withdrawal are not acceptable methods of contraception) 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 \< 30 mL/min * Significant history of neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent. * Any history of other active malignancies within 3 years prior to study en-try, with the exception of adequately treated in situ carcinoma of the cer-vix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically re-sected with curative intent. * Subject who has malabsorption syndrome or other condition which pre-cludes enteral route of administration. * Evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled and/or active systemic infection (viral, bac-terial or fungal) * Active HBV positive hepatitis * The following categories of patients HBV positive but with non evidence of active hepatitis may be considered for the study: * HBsAg positive with HBV DNA \< 2000 UI/ml (inactive carriers); HBV DNA \> 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 treatment 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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': "Study design This is an open-label, multi-center, single arm phase II trial, with a two-stage design, to evaluate the activity and safety of ABT-199 single agent in patients with BCL-2 pos R/R PTCL-NOS, AITL, TFH.\n\nA pre-screening evaluation of immunohistochemical positivity of BCL-2 will be performed in the relapse biopsy, if available, or otherwise in the initial biopsy. BCL-2 evaluation will be centralized (FIL Laboratories). Only patients with a percentage of BCL-2 positive tumor cells ≥ 25% will be included onto the study. Patients will receive ABT-199 until disease progression, unacceptable toxicity, withdrawal of consent and/or the investigator determines that further therapy is not in the patient's best interest. The primary objective of the study is ORR which will be evaluated after 3 cycles of treatment.", 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 22, 'type': 'ACTUAL'}}

2023-12-12