Use of Venetoclax as Single Agent in Patients With Relapsed/Refractory BCL-2 Positive Peripheral T Cell Lymphoma

• Status: Terminated
• Trial end date: 2020-12-02
• Target enrollment: 0
• Participant gender: All

Summary

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)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione Italiana Linfomi ONLUS
• Treatments: Venetoclax

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

• 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.